Pulmonary Nodules: growth rate assessment in patients by using serial CT and three-dimensional volumetry.

PURPOSE: To determine the precision of a three-dimensional (3D) method for measuring the growth rate of solid and subsolid nodules and its ability to detect abnormal growth rates. MATERIALS AND METHODS: This study was approved by the Institutional Research Board and was HIPAA compliant. Informed consent was waived. The growth rates of 123 lung nodules in 59 patients who had undergone lung cancer screening computed tomography (CT) were measured by using a 3D semiautomated computer-assisted volume method. Clinical stability was established with long-term CT follow-up (mean, 6.4 years±1.9 [standard deviation]; range, 2.0-8.5 years). A mean of 4.1 CT examinations per patient±1.2 (range, two to seven CT examinations per patient) was analyzed during 2.4 years±0.5 after baseline CT. Nodule morphology, attenuation, and location were characterized. The analysis of standard deviation of growth rate in relation to time between scans yielded a normative model for detecting abnormal growth. RESULTS: Growth rate precision increased with greater time between scans. Overall estimate for standard deviation of growth rate, on the basis of 939 growth rate determinations in clinically stable nodules, was 36.5% per year. Peripheral location (P=.01; 37.1% per year vs 25.6% per year) and adjacency to pleural surface (P=.05; 38.9% per year vs 34.0% per year) significantly increased standard deviation of growth rate. All eight malignant nodules had an abnormally high growth rate detected. By using 3D volumetry, growth rate-based diagnosis of malignancy was made at a mean of 183 days±158, compared with radiologic or clinical diagnosis at 344 days±284. CONCLUSION: A normative model derived from the variability of growth rates of nodules that were stable for an average of 6.4 years may enable identification of lung cancer.

Gene therapy in skin: choosing the optimal viral vector.

Skin is an ideal gene therapy target because it is readily accessible and is involved in many pathologic processes. Viruses are the most common gene vectors, however, few comparative studies exist examining their efficacy in skin. This study evaluates adenovirus serotype 5, adeno-associated virus type 2 and 5, MMLV-derived retrovirus, and human immunodeficiency virus-1 derived lentivirus for gene vector activity in human dermal fibroblasts and other skin cell lines. Human immunodeficiency virus-1-based lentiviral vector resulted in over 90% transduction in all cell lines tested. Transduced cells maintained reporter expression over several passages after a single exposure. In contrast, gene activity fell rapidly over cell divisions with adenoviral and adeno-associated vectors. Therefore, lentiviral vectors are the delivery mechanism of choice for long-term therapeutic gene expression in dermal fibroblasts and other skin cell lines, whereas adenoviral or adeno-associated vectors may be preferred for short-term therapy.

Postauricular cerebriform sebaceous nevus: case report and literature review.

Epidermal nevi are abnormal collections of cells derived from the embryonic epidermis. They are believed to represent cutaneous genetic mosaicism, with the histopathologic appearance related to mutations in genes involved in epidermal growth and differentiation. The clinical phenotype and potential inheritance are also related to these mutations and the time during embryogenesis when a mutation occurs. Since mutation timing in development is variable and the alleles are numerous, nevi have wide clinical variation. The lesions can be solitary, occur diffusely, or arise in association with other organ system abnormalities. Sebaceous nevus is a common subtype of epidermal nevi in which sebaceous gland-like structures predominate microscopically. Most lesions are alopecic, flat or slightly raised, and appear on the face and scalp. We review the presentation and treatment of a patient with an unusual appearing postauricular sebaceous nevus that was raised in a cerebriform appearing fashion, and discuss the related literature.

Dilated perivascular spaces: hallmarks of mild traumatic brain injury.

BACKGROUND AND PURPOSE: Recent animal and human studies have shown an increased frequency of enlarged, high-convexity Virchow-Robin spaces (VRS) in several neurologic diseases, suggesting their role as neuroradiologic markers of inflammatory changes. The aim of this study was to determine the prevalence of high-convexity dilated VRS in mild traumatic brain injury (TBI). METHODS: T2-weighted, T1-weighted, fluid-attenuated inversion recovery, and T2*-weighted gradient-echo brain MR images were acquired in 24 patients with TBI (10 women, 14 men; mean age, 33.6; range, 18.1-50.8 years) and 17 age- and sex-matched healthy control subjects (nine women, eight men; mean age, 32.8; range, 18.4-47.8 years). The mean interval after TBI was 3.6 days (range, 1-9 days) in 15 patients and 3.7 years (range, 0.6-13.4 years) in nine patients. Axial T2-weighted images were used to identify dilated VRS and to measure CSF volume; T1-weighted images were used to measure brain volume. Dilated VRS were identified as punctuate areas with CSF-like signal intensity in the high-convexity white matter. RESULTS: Mean (+/- standard deviation) number of VRS was significantly higher in patients (7.1 +/- 4.6) than in controls (3.0 +/- 3.0, P = 0.002) [corrected] In controls, VRS were associated with age (R = 0.69, P < .001) whereas in patients, they neither correlated with brain and CSF volumes nor with age and the elapsed time from injury. CONCLUSION: Our results suggest that the increased number of dilated VRS is a radiologic marker of mild head injury that is readily detectable on T2-weighted images. Because their number does not vary with time from injury, VRS probably reflect early and permanent brain changes.

A novel method for targeted gene therapy in ischemic tissues through viral transfection of an expression cassette containing multiple repetitions of hypoxia response element.

BACKGROUND: Increased levels of the transcription factor hypoxia inducible factor (HIF)-1 occur only in hypoxic tissue. The authors propose a therapeutic strategy that relies on HIF-1, the enhancer hypoxia response element (HRE), and the delivery vector adeno-associated virus-2 (AAV2) to direct ischemia specific gene therapy to skin. METHODS: An expression cassette containing the CMV promoter driving the reporter gene green fluorescent protein (GFP) was used to assess cutaneous tropism of AAV2. Transfection of dermal fibroblasts and immortalized keratinocytes (HaCat) was assessed with flow cytometry. Human embryonic kidney 293 (HEK) cells were used to produce vector stocks and test the authors' therapeutic strategy in quadruplicate. An expression cassette with nine repeats of HRE linked to beta-galactosidase (LacZ) within the AAV2 vector was constructed. HEK cells were transfected and exposed to normoxic (21% oxygen) and hypoxic (1% oxygen) conditions. LacZ activity was measured by conversion of galactoside red-beta-D-galactopyranoside. RESULTS: Approximately 50 percent of dermal fibroblasts and HaCat cells were transfected when treated with 1 x 10(4) genome copies/cell of AAV2-CMV-GFP. Using the same titration of AAV2-9HRE-LacZ, transfected HEK cells demonstrated LacZ activity of 0.496 +/- 0.068 U/microg in normoxia and 2.9 +/- 0.58 U/microg in hypoxia. Transfected cells exposed to 24 hours of hypoxia show greater than an 11-fold increase in LacZ activity (p < 0.05) compared with baseline normoxic controls. CONCLUSIONS: The authors' results confirm that AAV2 has in vitro tropism for skin-derived cell lines. Furthermore, HRE will drive gene expression in ischemia but not normoxia. This is the first step toward the authors' goal of HIF-1-regulated gene therapy to prevent ischemia related skin injury.

Effect of blood vessels on measurement of nodule volume in a chest phantom.

PURPOSE: To identify, by using a chest phantom, whether vessels that contact lung nodules measuring less than 5 mm in diameter will affect nodule volume assessment. MATERIALS AND METHODS: Forty synthetic nodules (20 with ground-glass attenuation and 20 with solid attenuation) that measured less than 5 mm in diameter were placed into a chest phantom either adjacent to (n = 30) or isolated from (n = 10) synthetic vessels. Nodules were imaged by using low-dose (20 mAs) and diagnostic (120 mAs) multi-detector row computed tomography (CT). Nodules that were known to lie in direct contact with vessels were confirmed by visual inspection. Nontargeted 1.25 x 1.00-mm sections were analyzed with a three-dimensional computer-assisted method for measuring nodule volume. A mixed-model analysis of variance was used to examine the influence of several factors (eg, the presence of adjacent vessels; tube current-time product; and nodule attenuation, diameter, and location) on measurement error. RESULTS: The mean absolute error (MAE) for all nodules adjacent to vessels was 2.3 mm(3), which was higher than the MAE for isolated nodules (1.9 mm(3)) (P < .001). This difference proved significant only for diagnostic CT (2.2 mm(3) for nodules adjacent to vessels vs 1.3 mm(3) for nodules isolated from vessels) (P < .05). A larger MAE was noted for nodules with ground-glass attenuation (2.3 mm(3)) versus those with solid attenuation (2.0 mm(3)), for increasing nodule volume (1.66 mm(3) for nodules smaller than 20 mm(3) vs 2.83 mm(3) for nodules larger than 40 mm(3)), and for posterior nodule location (P < .05). CONCLUSION: The presence of a vessel led to a small yet significant increase in volume error on diagnostic-quality images. This represents less than one-third of the overall error, even for nodules larger than 40 mm(3) or approximately 4 mm in diameter. This increase, however, may be more important for smaller nodules with errors of less than 3 mm(3).

Effect of CT image compression on computer-assisted lung nodule volume measurement.

PURPOSE: To evaluate the effect of two-dimensional wavelet-based computed tomographic (CT) image compression according to the Joint Photographic Experts Group (JPEG) 2000 standard on computer-assisted assessment of nodule volume. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the research board at the authors' institution; patients' informed consent was not required. Fifty-one nodules in 23 patients (seven men, 16 women; mean age, 59 years; age range, 39-75 years) were selected on low-dose CT scans that were compressed to levels of 10:1, 20:1, 30:1, and 40:1 by using a two-dimensional JPEG 2000 wavelet-based image compression method. Nodules were classified according to size (< or = 5 mm or > 5 mm in diameter), location (central, peripheral, or abutting pleura or fissures), and attenuation (solid, calcified, or subsolid). Regions of interest were placed on the original images and transposed onto compressed images. Nodule volumes on original (noncompressed) and compressed images were measured by using a computer-assisted method. A mixed-model analysis of variance was conducted for statistical evaluation. RESULTS: Nodule volumes averaged 388.1 mm3 (range, 34-3474 mm3). There were three calcified, 33 solid noncalcified, and 15 subsolid nodules (13 with ground-glass attenuation). Average volume decreased with increasing compression level, to 383 mm3 (10:1), 370 mm3 (20:1), 360 mm3 (30:1), and 354 mm3 (40:1). No significant difference was identified between measurements obtained on original images and those compressed to a level of 10:1. Significant differences were noted, however, between original images and those compressed to a level of 20:1 or greater (P < .05). Compression level significantly interacted with nodule size, location, and attenuation (P < .001). The effect of compression was greater for nodules with ground-glass attenuation than for those with higher attenuation values. The difference in mean volumes between original images and those compressed to a level of 20:1 was 34.9 mm3 for nodules with ground-glass attenuation, compared with 8.3 mm3 for higher-attenuation nodules, a 4.2-fold difference. CONCLUSION: Nodule volumes measured on images compressed to a level of 20:1 differed significantly from those measured on noncompressed images, especially for nodules with ground-glass attenuation. This difference could affect the assessment of nodule change in size as measured with computer-assisted methods.

Appendicitis in children: low-dose CT with a phantom-based simulation technique--initial observations.

PURPOSE: To retrospectively determine the accuracy of low-dose (20-mAs) computed tomography (CT) in the diagnosis of acute appendicitis in children by using a technique that enables the simulation of human CT scans acquired at a lower tube current given the image acquired at a standard dose. MATERIALS AND METHODS: Institutional review board approval was obtained, informed consent was not required, and the study was HIPAA compliant. The authors reviewed 100 standard-dose pediatric abdominal-pelvic CT scans (50 positive and 50 negative scans) obtained in 100 patients and corresponding simulated low-dose (20-mAs) scans. The standard-dose scans were obtained for evaluation in patients suspected of having appendicitis. Scans were reviewed in randomized order by four experienced pediatric radiologists. The patients with positive findings included 21 girls (mean age, 9.2 years) and 29 boys (mean age, 8.4 years). The patients with negative findings included 28 girls (mean age, 9.2 years) and 22 boys (mean age, 8.4 years). Simulation was achieved by adding noise patterns from repeated 20-mAs scans of a pediatric pelvis phantom to the original scans obtained with a standard tube current. Observers recorded their confidence in the diagnosis of appendicitis by using a six-point scale. Dose-related changes were analyzed with generalized estimating equations and the nonparametric sign test. RESULTS: There was a statistically significant (P < .001, sign test) decrease in both sensitivity and accuracy with a lower tube current, from 91.5% with the original tube current to 77% with the lower tube current. A low dose was the only statistically significant (P < .001) risk factor for a false-negative result. The specificity was unchanged at 94% for both the images obtained with the original tube current and the simulated low-dose images. The overall accuracy decreased from 92% with the original dose to 86% with the low dose. CONCLUSION: Preliminary findings indicate that it is feasible to optimize the CT dose used to evaluate appendicitis in children by using phantom-based computer simulations.