Georgeann McGuinness

Early Lung Cancer Action Project: overall design and findings from baseline screening

BACKGROUND The Early Lung Cancer Action Project (ELCAP) is designed to evaluate baseline and annual repeat screening by low-radiation-dose computed tomography (low-dose CT) in people at high risk of lung cancer. We report the baseline experience. METHODS ELCAP has enrolled 1000 symptom-free volunteers, aged 60 years or older, with at least 10 pack-years of cigarette smoking and no previous cancer, who were medically fit to undergo thoracic surgery. After a structured interview and informed consent, chest radiographs and low-dose CT were done for each participant. The diagnostic investigation of screen-detected non-calcified pulmonary nodules was guided by ELCAP recommendations, which included short-term high-resolution CT follow-up for the smallest non-calcified nodules. FINDINGS Non-calcified nodules were detected in 233 (23% [95% CI 21-26]) participants by low-dose CT at baseline, compared with 68 (7% [5-9]) by chest radiography. Malignant disease was detected in 27 (2.7% [1.8-3.8]) by CT and seven (0.7% [0.3-1.3]) by chest radiography, and stage I malignant disease in 23 (2.3% [1.5-3.3]) and four (0.4% [0.1-0.9]), respectively. Of the 27 CT-detected cancers, 26 were resectable. Biopsies were done on 28 of the 233 participants with non-calcified nodules; 27 had malignant non-calcified nodules and one had a benign nodule. Another three individuals underwent biopsy against the ELCAP recommendations; all had benign non-calcified nodules. No participant had thoracotomy for a benign nodule. INTERPRETATION Low-dose CT can greatly improve the likelihood of detection of small non-calcified nodules, and thus of lung cancer at an earlier and potentially more curable stage. Although false-positive CT results are common, they can be managed with little use of invasive diagnostic procedures.

CT of airways disease and bronchiectasis.

High-resolution CT is accepted as an accurate noninvasive means of diagnosing bronchiectasis. A wide spectrum of abnormalities may be identified at HRCT in patients with airway disease, including various distinctive patterns of bronchiectasis in specific clinical settings, such as ABPA, MAC infection, AIDS, and CF. Characteristic CT findings occasionally suggest a specific diagnosis that may not have been under clinical consideration. HRCT also provides significant clinical use in assessing the degree and extent of airway disease, and allows noninvasive monitoring of disease progression, regression, or response to therapy.

High Resolution Ct Findings in Miliary Lung Disease

High-resolution CT (HRCT) and chest radiographs were compared in nine patients with miliary lung disease. In all cases, miliary disease was documented to be infectious in etiology; six of these patients proved to be human immunodeficiency virus (HIV) positive. A mixture of both sharply and poorly defined 1-3 mm nodules was seen in all cases, many of the latter having an appearance indistinguishable from airspace nodules. Other features attributable to the presence of nodules included nodular interlobular septae, nodular irregularity of vessels, subpleural dots, and studded fissures. Diffuse intra- and interlobular septal thickening also proved common, seen in all but one case (91%). Based on limited HRCT-pathologic correlation, CT findings appear primarily to be due to granulomatous foci developing in a seemingly random distribution involving both pulmonary airspaces as well as the interstitium. It is concluded that in the appropriate clinical setting this constellation of findings is characteristic of miliary disease; the role of HRCT especially in the early diagnosis of miliary disease in HIV positive patients remains to be determined prospectively.

Volumetric (helical / spiral) CT (VCT) of the airways

Volumetric computed tomography (VCT) represents an important improvement over conventional CT for assessing most airway abnormalities. Elimination of misregistration due to variations in respiration coupled with decreased motion artifacts and the ability to obtain routine overlapping sections allow a more confident estimation of the presence and extent of disease. Recently, attention has focused on newer reconstruction techniques including: multiplanar reconstructions (MPRs), including curved multiplanar reformations; multiplanar volume reconstructions (MPVRs) using ray projection techniques, such as maximum and minimum projection imaging; external rendering, or 3D-shaded surface displays; and, most recently, internal rendering or so-called “virtual bronchoscopy”. Given the often redundant nature of many of these methodologies determining indications for their use remains to be established, especially by comparison to axial imaging. The purpose of this article is to review these various reconstruction techniques and, based on current knowledge, place them in an appropriate clinical context.

AIDS associated bronchiectasis : CT features

The occurrence of bronchiectasis has only rarely been noted among the protean manifestations of HIV infection in the lungs. We retrospectively identified bronchiectasis on CT scans in 12 HIV + and/or AIDS patients in the absence of either documented mycobacterial infection or a history of prior recurrent pyogenic infection. Pneumonitis was documented in 10 of 12 cases. In eight cases, bronchiectasis was associated with episodes of pyogenic infection; four of these patients also had documented opportunistic infections, including three cases of Pneumocystis carinii pneumonia (PCP). Two patients had infection due solely to PCP. In two cases, bronchiectasis was found in association with one case each of lymphocytic interstitial pneumonitis and nonspecific interstitial pneumonitis, respectively. Although the true incidence of bronchiectasis in this population remains to be established, in our experience bronchiectasis should be considered among the varied pulmonary manifestations of HIV infection. Furthermore, the seemingly rapid development and extent of bronchiectasis in this population suggest an accelerated form of the disease.

Variables affecting pulmonary nodule detection with computed tomography: evaluation with three-dimensional computer simulation.

To meaningfully evaluate factors determining the overall accuracy of computed tomography (CT) for identifying pulmonary nodules, computer-generated nodules were superimposed on normal CT scans and interpreted independently by three experienced chest radiologists. Variables evaluated included nodule size, shape, number, density, location, edge characteristics, and relationship to adjacent vessels, as well as technical factors, including slice thickness and electronic windowing. The overall sensitivity in identifying nodules was 62% and the specificity was 80%. On average, the observers identified 56, 67, and 63% of nodules on 1.5-, 5-, and 10-mm-thick sections, respectively (p = 0.037). Nodules were more difficult to identify on 1.5-mm-thick sections. On average, observers identified 1, 48, 82, and 91% of nodules <1.5, <3, <4.5, and <7 mm in diameter, respectively (p < 0.001). Other factors that made a significant contribution (p < 0.01) in identifying nodules, as determined by linear discriminant function analysis, included nodule location, angiocentricity, and density. We concluded that computer-generated nodules can be used to assess a large number of imaging variables. We anticipate that this approach will be of considerable utility in assessing the accuracy of interpretation of a wide range of pathologic entities as well as in optimizing three-dimensional scan protocols within the thorax.

Advantages of parallel imaging in conjunction with hyperpolarized helium—A new approach to MRI of the lung

Hyperpolarized helium (3He) gas MRI has the potential to assess pulmonary function. The non‐equilibrium state of hyperpolarized 3He results in the continual depletion of the signal level over the course of excitations. Under non‐equilibrium conditions the relationship between the signal‐to‐noise ratio (SNR) and the number of excitations significantly deviates from that established in the equilibrium state. In many circumstances the SNR increases or remains the same when the number of data acquisitions decreases. This provides a unique opportunity for performing parallel MRI in such a way that both the temporal and spatial resolution will increase without the conventional decrease in the SNR. In this study an analytical relationship between the SNR and the number of excitations for any flip angle was developed. Second, the point‐spread function (PSF) was utilized to quantitatively demonstrate the unconventional SNR behavior for parallel imaging in hyperpolarized gas MRI. Third, a 24‐channel (24ch) receive and two‐channel (2ch) transmit phased‐array system was developed to experimentally prove the theoretical predictions with 3He MRI. The in vivo experimental results prove that significant temporal resolution can be gained without the usual SNR loss in an equilibrium system, and that the entire lung can be scanned within one breath‐hold (∼13 s) by applying parallel imaging to 3D data acquisition. Magn Reson Med, 2006.

Diffusional kurtosis imaging in the lung using hyperpolarized 3He

Diseases of the small airspaces represent an increasingly important health problem. Asthma is primarily a disease of airway dysfunction, while chronic obstructive pulmonary disease (COPD) is associated with abnormalities in both the small airways and the alveoli. Conventional diffusion magnetic resonance imaging (MRI) of hyperpolarized noble gases, because of the short T2* of the gas, is only capable of monitoring diffusion over short times and hence only short distances. Diffusion imaging is therefore only sensitive to changes in small structures of the lung (primarily the alveoli), and will not adequately interrogate diffusion along the longitudinal axes of bronchi and bronchioles. In this communication we present a new method, termed diffusional kurtosis imaging (DKI), that is particularly sensitive to diffusion over longer distances. DKI may therefore be more sensitive to abnormalities in the bronchioles and bronchi than conventional diffusion imaging. Preliminary DKI measurements on healthy human subjects and one patient with symptoms suggestive of small airway disease are presented. Although the apparent diffusion coefficient (ADC) in the patient was similar to that in the normal controls, diffusional kurtosis was markedly reduced. This suggests that DKI measurements may be useful for assessing diseases of the small airways. Magn Reson Med, 2006.

Bronchiectasis: CT/clinical correlations

The association between bronchiectasis and human immunodeficiency virus infection, the resurgence of tuberculosis, especially in urban and immunocompromised patients, and the recognition of bronchiectasis as a manifestation of rejection in the transplant population are emerging clinical settings in which establishing the diagnosis of bronchiectasis is becoming increasingly important. High-resolution CT, by virtue of its well-established accuracy, is currently accepted as the optimal noninvasive means of diagnosing bronchiectasis. However, reliable diagnosis requires meticulous attention to technique and a thorough knowledge of potential pitfalls. These include, among others, respiratory and cardiac motion artifacts as well as effects of collimation and electronic windowing. It also is important to recognize diseases that may mimic the appearance of bronchiectasis as well as unusual manifestations of bronchiectasis that may obscure the diagnosis.

CT Scan Screening for Lung Cancer: Risk Factors for Nodules and Malignancy in a High-Risk Urban Cohort

Background Low-dose computed tomography (CT) for lung cancer screening can reduce lung cancer mortality. The National Lung Screening Trial reported a 20% reduction in lung cancer mortality in high-risk smokers. However, CT scanning is extremely sensitive and detects non-calcified nodules (NCNs) in 24–50% of subjects, suggesting an unacceptably high false-positive rate. We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant. Methods We performed a longitudinal lung cancer biomarker discovery trial (NYU LCBC) that included low-dose CT-screening of high-risk individuals over 50 years of age, with more than 20 pack-year smoking histories, living in an urban setting, and with a potential for asbestos exposure. We used case-control studies to identify risk factors associated with the presence of nodules (n = 625) versus no nodules (n = 557), and lung cancer patients (n = 30) versus benign nodules (n = 128). Results The NYU LCBC followed 1182 study subjects prospectively over a 10-year period. We found 52% to have NCNs >4 mm on their baseline screen. Most of the nodules were stable, and 9.7% of solid and 26.2% of sub-solid nodules resolved. We diagnosed 30 lung cancers, 26 stage I. Three patients had synchronous primary lung cancers or multifocal disease. Thus, there were 33 lung cancers: 10 incident, and 23 prevalent. A sub-group of the prevalent group were stable for a prolonged period prior to diagnosis. These were all stage I at diagnosis and 12/13 were adenocarcinomas. Conclusions NCNs are common among CT-screened high-risk subjects and can often be managed conservatively. Risk factors for malignancy included increasing age, size and number of nodules, reduced FEV1 and FVC, and increased pack-years smoking. A sub-group of screen-detected cancers are slow-growing and may contribute to over-diagnosis and lead-time biases.