CT reconstruction techniques for improved accuracy of lung CT airway measurement.

PURPOSE: To determine the impact of constrained reconstruction techniques on quantitative CT (qCT) of the lung parenchyma and airways for low x-ray radiation dose. METHODS: Measurement of small airways with qCT remains a challenge, especially for low x-ray dose protocols. Images of the COPDGene quality assurance phantom (CTP698, The Phantom Laboratory, Salem, NY) were obtained using a GE discovery CT750 HD scanner for helical scans at x-ray radiation dose-equivalents ranging from 1 to 4.12 mSv (12-100 mA s current-time product). Other parameters were 40 mm collimation, 0.984 pitch, 0.5 s rotation, and 0.625 mm thickness. The phantom was sandwiched between 7.5 cm thick water attenuating phantoms for a total length of 20 cm to better simulate the scatter conditions of patient scans. Image data sets were reconstructed using STANDARD (STD), DETAIL, BONE, and EDGE algorithms for filtered back projection (FBP), 100% adaptive statistical iterative reconstruction (ASIR), and Veo reconstructions. Reduced (half) display field of view (DFOV) was used to increase sampling across airway phantom structures. Inner diameter (ID), wall area percent (WA%), and wall thickness (WT) measurements of eight airway mimicking tubes in the phantom, including a 2.5 mm ID (42.6 WA%, 0.4 mm WT), 3 mm ID (49.0 WA%, 0.6 mm WT), and 6 mm ID (49.0 WA%, 1.2 mm WT) were performed with Airway Inspector (Surgical Planning Laboratory, Brigham and Women's Hospital, Boston, MA) using the phase congruency edge detection method. The average of individual measures at five central slices of the phantom was taken to reduce measurement error. RESULTS: WA% measures were greatly overestimated while IDs were underestimated for the smaller airways, especially for reconstructions at full DFOV (36 cm) using the STD kernel, due to poor sampling and spatial resolution (0.7 mm pixel size). Despite low radiation dose, the ID of the 6 mm ID airway was consistently measured accurately for all methods other than STD FBP. Veo reconstructions showed slight improvement over STD FBP reconstructions (4%-9% increase in accuracy). The most improved ID and WA% measures were for the smaller airways, especially for low dose scans reconstructed at half DFOV (18 cm) with the EDGE algorithm in combination with 100% ASIR to mitigate noise. Using the BONE + ASIR at half BONE technique, measures improved by a factor of 2 over STD FBP even at a quarter of the x-ray dose. CONCLUSIONS: The flexibility of ASIR in combination with higher frequency algorithms, such as BONE, provided the greatest accuracy for conventional and low x-ray dose relative to FBP. Veo provided more modest improvement in qCT measures, likely due to its compatibility only with the smoother STD kernel.

Elastin expression in very severe human COPD.

Alveolar elastic fibres are key targets of proteases during the pathogenesis of chronic obstructive pulmonary disease (COPD). In the current study, we hypothesised that a response to injury leads to enhanced alveolar elastin gene expression in very severe COPD. Lung samples obtained from 43 patients, including 11 with very severe COPD (stage 4), 10 donors, 10 with moderate/severe COPD (stage 2-3) and 12 non-COPD subjects, were analysed for elastin mRNA expression by real-time RT-PCR and in situ hybridisation. Alveolar elastic fibres were visualised using Hart's staining of sections of frozen inflated lungs obtained from 11 COPD stage 4 patients and three donor lungs. Compared with donors, non-COPD and stage 2-3 COPD, elastin mRNA expression was significantly increased in very severe COPD lungs (12-fold change), and localised in situ hybridisation induced elastin expression to alveolar walls. Compared with donors, alveolar elastic fibres also comprised a greater volume fraction of total lung tissue in very severe COPD lungs (p<0.01), but elastic fibre content was not increased per lung volume, and desmosine content was not increased. The present study demonstrates enhanced alveolar elastin expression in very severe COPD. The efficiency of this potential repair mechanism and its regulation remain to be demonstrated.

Creation of a CT Image Library for the Lung Screening Study of the National Lung Screening Trial.

The CT Image Library (CTIL) of the Lung Screening Study (LSS) network of the National Lung Screening Trial (NLST) consists of up to three annual screens using CT imaging from each of 17,308 participants with a significant history of smoking but no evidence of cancer at trial enrollment (Fall 2002-Spring 2004). Screens performed at numerous medical centers associated with 10 LSS-NLST screening centers are deidentified of protected health information and delivered to the CTIL via DVD, external hard disk, or Internet/Virtual Private Network transmission. The collection will be completed in late 2006. The CTIL is of potential interest to clinical researchers and software developers of nodule detection algorithms. Its attractiveness lies in its very specific, well-defined patient population, scanned via a common CT protocol, and in its collection of evenly spaced serial screens. In this work, we describe the technical details of the CTIL collection process from screening center retrieval through library storage.

CT of thoracic lymph nodes. Part II: diseases and pitfalls.

CT is the primary non-invasive technique for the diagnostic evaluation of thoracic lymph nodes. The CT patterns and anatomic location of thoracic lymph node involvement can provide important clues in the diagnosis of many diseases. Part I of the pictorial review illustrates the anatomic location and drainage of thoracic lymph nodes in the chest wall, mediastinum, and lungs through examples of pathologic involvement. Part II of the pictorial review focuses on CT patterns of lymph node involvement in various pulmonary and extrapulmonary diseases, differential diagnoses based on CT findings, and pitfalls.

CT of thoracic lymph nodes. Part I: anatomy and drainage.

CT is the primary non-invasive technique for the diagnostic evaluation of thoracic lymph nodes. The CT patterns and anatomic location of thoracic lymph node involvement can provide important clues in the diagnosis of many diseases. Part I of the pictorial review illustrates the anatomic location and drainage of thoracic lymph nodes in the chest wall, mediastinum and lungs through examples of pathologic involvement. Part II of the pictorial review focuses on CT patterns of lymph node involvement in various pulmonary and extrapulmonary diseases, differential diagnoses based on CT findings and pitfalls.

Repeatability of quantitative CT indexes of emphysema in patients evaluated for lung volume reduction surgery.

PURPOSE: To evaluate the repeatability of quantitative computed tomographic (CT) indexes of emphysema and the effect of spirometric gating of lung volume during CT in candidates for lung volume reduction surgery (LVRS). MATERIALS AND METHODS: Initial and same-day repeat routine inspiratory spiral chest CT studies were performed in 29 LVRS candidates (group 1, routine study vs repeat study). In a separate cohort of 29 LVRS candidates, spiral chest CT studies were performed both without and with spirometric gating by using a spirometer to trigger scanning at 90% of vital capacity (group 2, spirometric gating study). In each study, Pearson and intraclass correlation coefficients were calculated to determine the agreement between multiple pairs of whole-lung quantitative CT indexes of emphysema, and mean values were compared with two-tailed paired t tests. RESULTS: Pearson and intraclass correlation coefficients were high for all quantitative CT indexes (all > or = 0.92). No significant differences were found between mean values of quantitative CT indexes in group 1. Variation in quantitative CT results was small but more prominent in group 2 than in group 1. The variation in quantitative CT results was primarily related to differences in lung volume (r(2) as great as 0.83). CONCLUSION: Repeatability of quantitative CT test results in LVRS candidates is high and unlikely to improve by using spirometric gating.

MR imaging of diffusion of (3)He gas in healthy and diseased lungs.

Hyperpolarized (3)He gas MRI was used to form maps of the effective diffusivity of gas in human lungs. Images of diffusion as well as spin density are presented from a study of 11 healthy volunteers and 5 patients with severe emphysema. The effective rate of diffusion, D(e), of the gas is reduced by the alveolar walls; tissue destruction in emphysema is hypothesized to result in larger D(e). Indeed, the mean value of D(e) in the emphysematous lungs is found here to be about 2.5 times that of healthy lungs, although still smaller than the unrestricted diffusivity of (3)He in free air. Histograms of D(e) values across coronal slices are presented. The results are discussed in terms of spatial variations, variations among individuals, healthy and diseased, and variations due to changes in lung volume. Magn Reson Med 44:174-179, 2000.

Dynamic echo planar MR imaging of lung ventilation with hyperpolarized (3)He in normal subjects and patients with severe emphysema.

We applied the rapid imaging capability of echo planar MR pulse sequences and hyperpolarized (3)He ventilation imaging to observe the dynamic distribution of gas in the lungs during breathing. Findings in five normal volunteers (age 19-53 years) and four patients with severe smoking-related emphysema (age 56-71 years) were compared. All studies were performed on a 1.5 T whole body scanner using a 30 cm Helmholtz surface coil and 0.5 l of 20-40% polarized (3)He mixed with 1-2 l nitrogen. Our echo planar imaging pulse sequence allowed acquisition of each image in 0.04 s, with a pixel size of 7 mm(2) (TR = 40.5 ms, TE = 12.1 ms, flip angle = 22 degrees, echo train length = 32, matrix = 32 x 64, field of view = 225 x 450 mm, slice thickness = 10 mm). Imaging was performed in the transaxial plane repeatedly at 3, 10 or 20 evenly spaced levels, immediately before and during breathing of the gas mixture. In normal subjects during the first breath, (3)He appeared throughout each slice first in the mid lungs, then in the lower lungs, then in the upper lungs, with slightly greater signal in the dependent posterior regions. In patients with emphysema, sequential filling of different lung regions was seen during the first breath, with delayed filling of other regions observed during rebreathing and room air washout. We conclude that subsecond dynamic (3)He MR ventilation imaging can reveal normal and abnormal ventilation phenomena not seen with conventional scintigraphic methods, and offers another approach to the study of ventilation physiology and pathophysiology.

Patient selection for lung volume reduction surgery: An objective model based on prior clinical decisions and quantitative CT analysis.

OBJECTIVES: We used whole-lung quantitative CT analysis (QCT)-an objective method of evaluating emphysema severity and distribution based on measurement of lung density-to determine whether subjective selection criteria for lung volume reduction surgery are applied consistently and to model the patient selection process, and assessed the relationship of the model to postoperative outcome. DESIGN: Logistic regression analysis using QCT indexes of emphysema and preoperative physiologic test results as the independent variables, and the decision to operate as the dependent variable. SETTING: University hospital. PATIENTS: Seventy patients selected for bilateral lung volume reduction surgery and 32 otherwise operable patients excluded from surgery based on subjective assessment of emphysema morphology on chest radiography, CT, and perfusion scintigraphy. INTERVENTION: Bilateral lung volume reduction surgery in the selected group. MEASUREMENTS AND RESULTS: Emphysema in patients selected for surgery was more severe overall and in the upper lungs by multiple QCT indexes (p < 0.01, unpaired two-tailed t test). Physiologic abnormalities were slightly more severe in selected patients (p < 0.05, unpaired two-tailed t test). The range of many QCT and physiologic values overlapped considerably between the selected and excluded groups. The percent severe emphysema (<- 960 Hounsfield units [HU]), upper/lower lung emphysema ratio (- 900 HU threshold), and residual volume were the key variables in the model predicting selection decisions (model r(2) = 0.48; p < 0.0001). The model correctly predicted selection decisions in 87% of all cases, 91% of the selected group, and 78% of the excluded group. Surgical patients with a higher model-derived probability of selection had greater postoperative improvement in FEV(1) and 6-min walk distance. CONCLUSIONS: Radiologic selection criteria are applied consistently to the majority of patients. QCT features are strongly associated with selection decisions, are related to outcome, and may help improve consistency and confidence in patient selection.

Rapid imaging of hyperpolarized gas using EPI.

Rapid repetitive MRI of hyperpolarized (HP) gases using echo-planar imaging (EPI) has been theoretically investigated and experimentally demonstrated for (3)He in human lung. A quantitative treatment of signal attenuation and magnetization consumption for the unique circumstance of a rapidly diffusing nonrenewable magnetization source has been performed. Rapid (compared to the human respiratory cycle) and repetitive imaging of the lung gas space with EPI and a single delivered bolus of HP-(3)He is feasible using low flip angles, provided the voxels are not too small. A coarse-grid (32 x 64) EPI pulse sequence has been developed and implemented to image the lungs of healthy volunteers during rebreathing of a HP-(3)He/N(2) gas mixture. A set of three 10-mm axial slices was imaged every 0.12 sec for the 36 sec duration of rebreathing, yielding a real-time visualization of ventilation. Despite some mild artifacts, the images are of good quality and show changes in gas density related to respiratory physiology. Magn Reson Med 42:507-514, 1999.

Gadolinium as a CT contrast agent: assessment in a porcine model.

PURPOSE: To investigate the use of gadolinium as a computed tomographic (CT) contrast agent. MATERIALS AND METHODS: In vitro attenuation measurements of multiple dilutions of gadodiamide and ioversol were compared. In three pigs, 50-mL boluses of undiluted gadodiamide were injected intravenously at 2 mL/sec, and repeated single-level scans were obtained through the lung bases, liver, and kidneys. The doses of 0.8-1.0 mmol of gadolinium per kilogram of body weight were approximately three times the highest doses currently used in patients. Enhancement was determined from attenuation measurements in the aorta, pulmonary arteries, liver, and kidneys. RESULTS: In vitro, the attenuation of undiluted gadodiamide (3,069 HU) was equivalent to that of ioversol diluted to 106 mg of iodine per milliliter and at equimolar concentrations was 50% greater than that of ioversol. The magnitude of and time to peak enhancement were 141 HU and 27 seconds (n = 3) for the aorta; 168 HU and 21 seconds (n = 3) for the pulmonary arteries; 23 HU and 65 seconds (n = 2) for the liver; and 63 HU and 32 seconds (n = 1) for the kidneys. Time-attenuation curves revealed a useful duration of enhancement of 20-30 seconds for the aorta and pulmonary arteries. CONCLUSION: Gadolinium produces good vascular enhancement, adequate renal enhancement, and suboptimal hepatic enhancement. Further study is needed to determine the safety of the gadolinium dose required to produce similar enhancement in patients.

Imaging evaluation of the diaphragm.

The diaphragm performs most of the physiologic work of inspiration, and forms an anatomic barrier between the thoracic and abdominal cavities. Disorders of the diaphragm can be related to impairment of either of these functions, and most have radiologic manifestations. Both intrathoracic and intra-abdominal disease processes can alter the normal radiologic appearance of the diaphragm. Abnormalities are usually first detected on chest radiographs, often incidentally in asymptomatic patients, and many require further characterization by other imaging studies for definitive diagnosis. Fluoroscopy, CT, and MR imaging are frequently the most useful additional studies, whereas ultrasonography, barium contrast studies, and liver-spleen scintigraphy are occasionally helpful. Selection of the most appropriate radiologic technique in a given clinical situation can greatly facilitate the diagnosis of diaphragm abnormalities.

MR analysis of lung volume and thoracic dimensions in patients with emphysema before and after lung volume reduction surgery.

OBJECTIVE: This study was performed to assess the accuracy of determining lung volume in patients with emphysema using MR imaging and then to investigate changes in thoracic dimensions after lung volume reduction surgery. SUBJECTS AND METHODS: Fast gradient-echo breath-hold MR imaging through the entire thorax at full inspiration and expiration was performed in 21 patients with severe emphysema and was performed again in nine of the patients who underwent surgery. Lung volumes were determined using a semiautomated computerized method of delineating the lungs and summing cross-sectional areas. These summed areas were compared with volumes measured on plethysmography and CT. Postoperative changes in thoracic structure were determined by measuring anteroposterior and transverse lung dimensions and lung height before and after surgery. RESULTS: The correlation coefficients and SEM for determining inspiratory lung volume were MR imaging versus plethysmography, r = .77, SEM = -12% (volume measured as less on MR imaging); CT versus plethysmography, r = .86, SEM = -13% (volume measured as less on CT); and MR imaging versus CT, r = .87, SEM = 4% (volume measured as greater on MR imaging). The correlation coefficients and SEM for determining expiratory volume on MR imaging versus plethysmography were r = .77, SEM = 6% (volume measured as greater on MR imaging). After surgery, decreases were found in all thoracic dimensions, and such decreases were greatest at expiration. CONCLUSION: MR measurements of lung volume are comparable with those of CT and differ from those of plethysmography. Changes in thoracic dimensions after lung volume reduction surgery are consistent with improved respiratory mechanics.

Preoperative and postoperative imaging in the surgical management of pulmonary emphysema.

For patients with emphysema, imaging studies have been useful for diagnostic purposes and for preoperative patient selection for surgical intervention, such as bullectomy, lung transplantation, and LVRS. Chest radiography is useful in evaluating hyperinflation. Inspiratory and expiratory films are used to estimate diaphragmatic excursion and air-trapping. CT scan is used to evaluate the anatomy and distribution of emphysema throughout the lungs, providing information clinically unobtainable by other means. Both imaging techniques are useful for detecting other disease processes. Radionuclide lung scanning also provides an estimate of target areas, volume occupying but nonfunctioning lung. Cohort studies utilizing these imaging techniques have demonstrated associations between preoperative characteristics and postoperative outcome. The imaging studies, especially the chest radiograph, have also played an important role in postoperative management. Many other imaging options are available, such as HRCT scan, quantitative CT scan, and single photon emission CT scan. Other techniques, such as MR imaging, may play a future role as well.

Pulmonary emphysema: comparison of preoperative quantitative CT and physiologic index values with clinical outcome after lung-volume reduction surgery.

PURPOSE: To compare quantitative computed tomographic (CT) and preoperative physiologic values in emphysema with outcome after lung-volume reduction surgery. MATERIALS AND METHODS: In 46 patients, emphysema was quantified by measuring lung attenuation on preoperative CT scans. Quantitative CT and preoperative physiologic values and postoperative outcomes (1-second forced expiratory volume, PaO2, and 6-minute walk distance) were compared. RESULTS: Moderately strong correlations were found between several quantitative CT and preoperative physiologic values (magnitude of r = .29-.58, P < .05) and several quantitative CT and outcome measures (magnitude of r = .31-.47, P < .05). With stratification, postoperative outcome was better with mean lung attenuation greater than -900 HU; 75% or greater of upper lung below -900 HU (emphysema index); greater than 25% of lung below -960 HU (severe emphysema index); ratio of upper- and lower-lung emphysema indexes 1.5 or greater; volume of normally attenuated lung (-850 to -701 HU) greater than 1 L; and full width at half maximum of attenuation-frequency distribution 80 HU or less. Differences in outcome measures between groups stratified with quantitative CT values were often two- to threefold; patients with greater numbers of favorable quantitative CT values had better outcome. Correlations between preoperative physiologic measures and outcome were few. CONCLUSION: In emphysema, quantitative CT values correlate with outcome. Quantitative assessment of emphysema in candidates for lung-volume reduction surgery is potentially useful.

Perfusion scintigraphy in the evaluation for lung volume reduction surgery: correlation with clinical outcome.

PURPOSE: To identify preoperative pulmonary perfusion scintigraphic findings that might be associated with clinical outcomes after lung volume reduction surgery. MATERIALS AND METHODS: Preoperative perfusion scintigrams in 103 patients (56 men, 47 women; age range, 41-76 years; mean age, 61 years +/- 9) were reviewed and graded for emphysematous heterogeneity (from isolated areas to diffuse distribution), extent of maximally perfused lung, and lobar predominance (upper-lobe vs lower-lobe asymmetry). These findings were correlated with clinical outcome on the basis of pulmonary function, arterial blood gas levels, and exercise test results before and 6 months after surgery. RESULTS: Among the 96 patients who survived surgery, there was an average improvement of 47% in the forced expiratory volume in 1 second (FEV1), of 20% in arterial oxygen tension, and of 20% in the 6-minute walking distance. Scintigraphic markers correlated best with FEV1 improvement. The strongest scintigraphic predictor of increase in FEV1 was upper-lobe predominance (r = .38, P < .001), which was followed by heterogeneity (r = .31, P = .002). The seven patients who died had a significantly lower percentage of maximally perfused lung than the survivors (25% vs 34%, P = .004). CONCLUSION: Perfusion scintigraphy can provide modest prognostic information in patients who undergo evaluation for lung volume reduction surgery.

Lung volume reduction surgery: comparison of preoperative radiologic features and clinical outcome.

PURPOSE: To examine the relationship between preoperative radiologic findings and clinical outcome after lung volume reduction surgery. MATERIALS AND METHODS: In 50 consecutive patients, preoperative chest radiographs and computed tomographic (CT) scans were scored by four radiologists for features related to the severity and distribution of emphysema and compared with clinical improvement in forced expiratory volume in 1 second (FEV1), arterial partial pressure of oxygen, and exercise tolerance 6 months after surgery. RESULTS: In the 47 surviving patients, follow-up data showed greater postoperative improvement in function in patients with a global pattern of predominantly upper-lobe emphysema (P < .05) and in patients with a more heterogeneous distribution of emphysema, compressed lung, and a larger percentage of normal and mildly emphysematous lung (P < .05 for improvement in FEV1). Radiographic scores for individual features were more strongly correlated with outcome than CT scores. The combination of upper-lobe severity and percentage of normal and mildly emphysematous lung at CT were the strongest predictors of improvement in FEV1 (r2 = .49). The three patients who died were older (P = .05) and had more severe, diffuse emphysema compared with other patients. CONCLUSION: Imaging studies may help predict the degree of improvement and therefore should be considered an integral part of an objective patient selection process. Radiography alone may be adequate for initial screening.

Patients with emphysema: quantitative CT analysis before and after lung volume reduction surgery. Work in progress.

PURPOSE: To quantitatively assess the morphologic changes in the lungs after lung volume reduction surgery and determine whether changes at quantitative computed tomography (CT) reflect changes in lung function. MATERIALS AND METHODS: In 10 patients, chest CT images were obtained at full inspiration and expiration before and after surgery. A semiautomated segmentation method was developed to isolate the lung regions and calculate the lung volumes and frequency distribution of attenuation values. The changes in lung volume and attenuation after surgery were compared with clinical findings, and an exploratory evaluation of outcome predictors was conducted. RESULTS: Semiautomated segmentation and quantitative analysis compared favorably with manual techniques, and there was good correlation between the emphysema indexes and percentage predicted forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity, and diffusing capacity. The emphysema index decreased from 60% to 38% at inspiration and from 60% to 27% at expiration after surgery. The average CT lung volume decreased from 7.5 to 5.6 L at inspiration (25%) and from 6.4 to 3.8 L (41%) at expiration after surgery and correlated well with measurements at plethysmography. CONCLUSION: Substantial decreases in the lung volumes and emphysema index, increased airflow, possible reexpansion of some remaining lung, and the relation between preoperative quantitative CT indexes and clinical outcome suggest a multifactorial mechanism for improvement seen after surgery.

Chest radiography: depiction of normal anatomy and pathologic structures with selenium-based digital radiography versus conventional screen-film radiography.

PURPOSE: To compare the subjective visibility of normal anatomy and pathologic structures in the chest on conventional screen-film radiographs versus selenium-based digital radiographs. MATERIALS AND METHODS: Screen-film and digital standard posteroanterior (PA) and lateral chest radiographs were obtained in 49 patients (32 men, 17 women; mean age, 60 years; range, 24-91 years) undergoing chest computed tomography (CT). Conventional images were phototimed at 115 kVp with use of a wide-latitude screen-film system and an antiscatter grid. Digital images were obtained at 150 kVp with use of a commercial system with a selenium detector and an air gap alone for scatter reduction. The image sets were independently compared by four radiologists, and the relative visibility of anatomic and pathologic features (proved at CT) was graded. Statistical significance (P < .0028) was evaluated with a one-tailed t test. RESULTS: Visibility with the digital images was statistically significantly increased for 11 of 13 normal anatomic features and for pathologic structures in the lung, soft tissue, and bone. CONCLUSION: Subjective visibility of pathologic structures and most normal anatomic features in the thorax was statistically significantly improved with selenium-based digital chest radiography compared with conventional screen-film chest radiography.