Matthew D. Gilman

ACTIVATION OF A DROSOPHILA JANUS KINASE (JAK) CAUSES HEMATOPOIETIC NEOPLASIA AND DEVELOPMENTAL DEFECTS

In mammals, many cytokines and growth factors stimulate members of the Janus kinase (JAK) family to transduce signals for the proliferation and differentiation of various cell types, particularly in hematopoietic lineages. Mutations in the Drosophila hopscotch (hop) gene, which encodes a JAK, also cause proliferative defects. Loss‐of‐function alleles result in lethality and underproliferation of diploid tissues of the larva. A dominant gain‐of‐function allele, Tumorous‐lethal (hopTum‐l), leads to formation of melanotic tumors and hypertrophy of the larval lymph glands, the hematopoietic organs. We show that a single amino acid change in Hop is associated with the hopTum‐l mutation. Overexpression of either wild‐type hop or hopTum‐l in the larval lymph glands causes melanotic tumors and lymph gland hypertrophy indistinguishable from the original hopTum‐l mutation. In addition, overexpression of Hop in other tissues of the larva leads to pattern defects in the adult or to lethality. Finally, overexpression of either hop or hopTum‐l in Drosophila cell culture results in tyrosine phosphorylation of Hop protein. However, overexpression of hopTum‐l results in greater phosphorylation than overexpression of the wild‐type. We conclude that hopTum‐l encodes a hyperactive Hop kinase and that overactivity of Hop in lymph glands causes malignant neoplasia of Drosophila blood cells.

Adaptive Statistical Iterative Reconstruction Technique for Radiation Dose Reduction in Chest CT: A Pilot Study

PURPOSE To compare lesion detection and image quality of chest computed tomographic (CT) images acquired at various tube current-time products (40-150 mAs) and reconstructed with adaptive statistical iterative reconstruction (ASIR) or filtered back projection (FBP). MATERIALS AND METHODS In this Institutional Review Board-approved HIPAA-compliant study, CT data from 23 patients (mean age, 63 years ± 7.3 [standard deviation]; 10 men, 13 women) were acquired at varying tube current-time products (40, 75, 110, and 150 mAs) on a 64-row multidetector CT scanner with 10-cm scan length. All patients gave informed consent. Data sets were reconstructed at 30%, 50%, and 70% ASIR-FBP blending. Two thoracic radiologists assessed image noise, visibility of small structures, lesion conspicuity, and diagnostic confidence. Objective noise and CT number were measured in the thoracic aorta. CT dose index volume, dose-length product, weight, and transverse diameter were recorded. Data were analyzed by using analysis of variance and the Wilcoxon signed rank test. RESULTS FBP had unacceptable noise at 40 and 75 mAs in 17 and five patients, respectively, whereas ASIR had acceptable noise at 40-150 mAs. Objective noise with 30%, 50%, and 70% ASIR blending (11.8 ± 3.8, 9.6 ± 3.1, and 7.5 ± 2.6, respectively) was lower than that with FBP (15.8 ± 4.8) (P < .0001). No lesions were missed on FBP or ASIR images. Lesion conspicuity was graded as well seen on both FBP and ASIR images (P < .05). Mild pixilated blotchy texture was noticed with 70% blended ASIR images. CONCLUSION Acceptable image quality can be obtained for chest CT images acquired at 40 mAs by using ASIR without any substantial artifacts affecting diagnostic confidence. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101450/-/DC1.

Diffuse Lung Disease: CT of the Chest with Adaptive Statistical Iterative Reconstruction Technique

PURPOSE To compare visualization of subtle normal and abnormal findings at computed tomography (CT) of the chest for diffuse lung disease with images reconstructed with filtered back projection and adaptive statistical iterative reconstruction (ASIR) techniques. MATERIALS AND METHODS In this HIPAA-compliant, institutional review board-approved study, 24 patients underwent 64-section multi-detector row CT of the chest for evaluation of diffuse lung disease. Scanning parameters included a pitch of 0.984:1 and 120 kVp in thin-section mode, with 2496 views per rotation compared with 984 views acquired for normal mode. The 0.625-mm-thick images were reconstructed with filtered back projection, ASIR, and ASIR high-definition (ASIR-HD) kernels. Two thoracic radiologists independently assessed the filtered back projection, ASIR, and ASIR-HD images for small anatomic details (interlobular septa, centrilobular region, and small bronchi and bronchioles), abnormal findings (reticulation, tiny nodules, altered attenuation, bronchiectasis), image quality (graded by using a six-point scale, where 1 = excellent image quality, and 5 = interpretation impossible), image noise, and artifacts. Data were tabulated for statistical testing. RESULTS For visualization of normal and pathologic structures, CT image series reconstructed with ASIR-HD were rated substantially better than those reconstructed with filtered back projection and ASIR (P < .001). ASIR-HD images were superior to filtered back projection images in 15 of 24 (62%) patients for visualization of normal structures and in 24 of 24 (100%) patients for pathologic findings. ASIR-HD was superior to ASIR in three of 24 (12%) images for normal anatomic findings and in seven of 24 (29%) images for pathologic evaluation. None of the images in the three groups were rated as unacceptable for noise (P < .001). CONCLUSION ASIR-HD reconstruction results in superior visualization of subtle and tiny anatomic structures and lesions in diffuse lung disease compared with ASIR and filtered back projection reconstructions.

Diffuse Cystic Lung Disease at High-Resolution CT

OBJECTIVE This article will illustrate and describe the spectrum of diseases associated with air cysts at high-resolution CT (HRCT). CONCLUSION HRCT is an important modality in the evaluation of interstitial lung disease to include cystic lung disease. Although most commonly associated with lymphangioleiomyomatosis or Langerhans cell histiocytosis, cystic lung disease is increasingly being recognized as a feature of other entities. Awareness of the spectrum of HRCT findings associated with these diseases may help the trained observer narrow the differential diagnosis.

Optimal CT breathing protocol for combined thoracic PET/CT

OBJECTIVE The objective of this study was to determine the optimal breathing protocol for combined PET/CT scans of the thorax. SUBJECTS AND METHODS Eighty combined PET/CT scans were obtained in 64 patients (30 women, 34 men; mean age, 57 years; range, 19-86 years). The 80 PET/CT scans consisted of five group of patients (16 PET/CT scans per group) who underwent whole-body combined 18F-FDG PET/CT with different CT breathing protocols: expiration, mid suspended breath-hold, quiet breathing, small breath in, and regular breath in. The quality of alignment was analyzed at the diaphragm, aortic arch, heart, thoracic spine, and lung apices using a scale of ratings from 1 (very poor) to 5 (excellent). The Kruskal-Wallis test was used to compare alignment between breathing protocols for each anatomic reference point. RESULTS Alignment of the PET and CT data sets was excellent with three breathing protocols: expiration, mid suspended breath-hold, and quiet breathing, with no statistical differences. Significant misalignment occurred at the diaphragm (p < 0.0001) and heart (p < 0.0001) with the small breath-in and regular breath-in techniques. CONCLUSION Excellent image fusion of combined PET/CT data sets in the thorax, especially at the diaphragm and heart, can be achieved with expiration, mid suspended breath-hold, or quiet breathing. Quiet breathing is recommended for optimal patient comfort during acquisition of attenuation-correction CT data sets.

Computed tomography (CT) of the chest at less than 1 mSv: an ongoing prospective clinical trial of chest CT at submillisievert radiation doses with iterative model image reconstruction and iDose4 technique.

Purpose To assess lesion detection and diagnostic confidence of computed tomography (CT) of the chest performed at less than 1 mSv with 2 iterative reconstruction (IR) techniques. Materials and Methods Ten patients gave written informed consent for the acquisitions of images at submillisievert dose (0.9 mSv), in addition to clinical standard-dose (SD) chest CT (2.9 mSv). Submillisievert images were reconstructed with iDose4 and iterative model reconstruction (IMR). Two radiologists assessed lesion detection, margins, diagnostic confidence, and visibility of small structures. Objective noise and noise spectral density were measured. Results Lesion detection was identical for standard-dose filtered back projection (FBP), submSv iDose4, and submSv IMR. Lesion margins were better seen for 30% of detected lung lesions with submSv IMR compared to standard-dose FBP and submSv iDose4 (P < 0.05). Visibility of abdominal structures, and diagnostic confidence with submSv iDose4 and submSv IMR were similar to standard-dose FBP. There was 21% to 64% noise reduction with submSv IMR and 1% to 15% higher noise with iDose4 compared to standard-dose FBP (P < 0.0001). Conclusions Submillisievert IMR improves delineation of lesion margins compared to standard-dose FBP and submSv iDose4.

The 10 Pillars of Lung Cancer Screening: Rationale and Logistics of a Lung Cancer Screening Program

On the basis of the National Lung Screening Trial data released in 2011, the U.S. Preventive Services Task Force made lung cancer screening (LCS) with low-dose computed tomography (CT) a public health recommendation in 2013. The Centers for Medicare and Medicaid Services (CMS) currently reimburse LCS for asymptomatic individuals aged 55-77 years who have a tobacco smoking history of at least 30 pack-years and who are either currently smoking or had quit less than 15 years earlier. Commercial insurers reimburse the cost of LCS for individuals aged 55-80 years with the same smoking history. Effective care for the millions of Americans who qualify for LCS requires an organized step-wise approach. The 10-pillar model reflects the elements required to support a successful LCS program: eligibility, education, examination ordering, image acquisition, image review, communication, referral network, quality improvement, reimbursement, and research frontiers. Examination ordering can be coupled with decision support to ensure that only eligible individuals undergo LCS. Communication of results revolves around the Lung Imaging Reporting and Data System (Lung-RADS) from the American College of Radiology. Lung-RADS is a structured decision-oriented reporting system designed to minimize the rate of false-positive screening examination results. With nodule size and morphology as discriminators, Lung-RADS links nodule management pathways to the variety of nodules present on LCS CT studies. Tracking of patient outcomes is facilitated by a CMS-approved national registry maintained by the American College of Radiology. Online supplemental material is available for this article.

CT of Diffuse Tracheal Diseases

AJR:196, March 2011 both relapsing polychondritis and tracheobronchopathia osteochondroplastica. However, the presence of focal coarse calcification and ossification is highly suggestive of tracheobronchopathia osteochondroplastica rather than relapsing polychondritis. 7. Nodular calcification of the trachea is common in tracheobronchopathia osteochondroplastica and amyloidosis. However, amyloidosis tends to involve the airway concentrically, as opposed to tracheobronchopathia osteochondroplastica which spares the posterior wall. 8. Wegener granulomatosis most often affects the subglottic trachea but can be diffuse or multifocal. 9. Mounier-Kuhn syndrome is unique among the diffuse tracheal diseases in that it results in diffuse airway dilatation. Diverticula project between the cartilaginous rings giving the trachea and proximal bronchi a corrugated appearance.

Lymphomatoid Granulomatosis: CT and FDG-PET Findings

Objective Lymphomatoid granulomatosis (LG) is a rare, aggressive extranodal Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disease. The purpose of our study was to analyze the CT and fluorodeoxyglucose positron emission tomography (FDG-PET) findings of pulmonary LG. Materials and Methods Between 2000 and 2009, four patients with pathologically proven pulmonary LG and chest CT were identified. Two of these patients also had FDG-PET. Imaging features of LG on CT and PET were reviewed. Results Pulmonary nodules or masses with peribronchovascular, subpleural, and lower lung zonal preponderance were present in all patients. Central low attenuation (4 of 4 patients), ground-glass halo (3 of 4 patients), and peripheral enhancement (4 of 4 patients) were observed in these nodules and masses. An air-bronchogram and cavitation were seen in three of four patients. FDG-PET scans demonstrated avid FDG uptake in the pulmonary nodules and masses. Conclusion Pulmonary LG presents with nodules and masses with a lymphatic distribution, as would be expected for a lymphoproliferative disease. However, central low attenuation, ground-glass halo and peripheral enhancement of the nodules/masses are likely related to the angioinvasive nature of this disease. Peripheral enhancement and ground-glass halo, in particular, are valuable characteristic not previously reported that can help radiologists suggest the diagnosis of pulmonary LG.

Is Weight-Based Adjustment of Automatic Exposure Control Necessary for the Reduction of Chest CT Radiation Dose?

Objective To assess the effects of radiation dose reduction in the chest CT using a weight-based adjustment of the automatic exposure control (AEC) technique. Materials and Methods With Institutional Review Board Approval, 60 patients (mean age, 59.1 years; M:F = 35:25) and 57 weight-matched patients (mean age, 52.3 years, M:F = 25:32) were scanned using a weight-adjusted AEC and non-weight-adjusted AEC, respectively on a 64-slice multidetector CT with a 0.984:1 pitch, 0.5 second rotation time, 40 mm table feed/rotation, and 2.5 mm section thickness. Patients were categorized into 3 weight categories; < 60 kg (n = 17), 60-90 kg (n = 52), and > 90 kg (n = 48). Patient weights, scanning parameters, CT dose index volumes (CTDIvol) and dose length product (DLP) were recorded, while effective dose (ED) was estimated. Image noise was measured in the descending thoracic aorta. Data were analyzed using a standard statistical package (SAS/STAT) (Version 9.1, SAS institute Inc, Cary, NC). Results Compared to the non-weight-adjusted AEC, the weight-adjusted AEC technique resulted in an average decrease of 29% in CTDIvol and a 27% effective dose reduction (p < 0.0001). With weight-adjusted AEC, the CTDIvol decreased to 15.8, 15.9, and 27.3 mGy for the < 60, 60-90 and > 91 kg weight groups, respectively, compared to 20.3, 27.9 and 32.8 mGy, with non-weight-adjusted AEC. No significant difference was observed for objective image noise between the chest CT acquired with the non-weight-adjusted (15.0 ± 3.1) and weight-adjusted (16.1 ± 5.6) AEC techniques (p > 0.05). Conclusion The results of this study suggest that AEC should be tailored according to patient weight. Without weight-based adjustment of AEC, patients are exposed to a 17 - 43% higher radiation-dose from a chest CT.