John R. Mayo

Small-Airway Obstruction and Emphysema in Chronic Obstructive Pulmonary Disease

BACKGROUND The major sites of obstruction in chronic obstructive pulmonary disease (COPD) are small airways (<2 mm in diameter). We wanted to determine whether there was a relationship between small-airway obstruction and emphysematous destruction in COPD. METHODS We used multidetector computed tomography (CT) to compare the number of airways measuring 2.0 to 2.5 mm in 78 patients who had various stages of COPD, as judged by scoring on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) scale, in isolated lungs removed from patients with COPD who underwent lung transplantation, and in donor (control) lungs. MicroCT was used to measure the extent of emphysema (mean linear intercept), the number of terminal bronchioles per milliliter of lung volume, and the minimum diameters and cross-sectional areas of terminal bronchioles. RESULTS On multidetector CT, in samples from patients with COPD, as compared with control samples, the number of airways measuring 2.0 to 2.5 mm in diameter was reduced in patients with GOLD stage 1 disease (P=0.001), GOLD stage 2 disease (P=0.02), and GOLD stage 3 or 4 disease (P<0.001). MicroCT of isolated samples of lungs removed from patients with GOLD stage 4 disease showed a reduction of 81 to 99.7% in the total cross-sectional area of terminal bronchioles and a reduction of 72 to 89% in the number of terminal bronchioles (P<0.001). A comparison of the number of terminal bronchioles and dimensions at different levels of emphysematous destruction (i.e., an increasing value for the mean linear intercept) showed that the narrowing and loss of terminal bronchioles preceded emphysematous destruction in COPD (P<0.001). CONCLUSIONS These results show that narrowing and disappearance of small conducting airways before the onset of emphysematous destruction can explain the increased peripheral airway resistance reported in COPD. (Funded by the National Heart, Lung, and Blood Institute and others.).

Noninvasive Evaluation of the Aortic Root With Multislice Computed Tomography : Implications for Transcatheter Aortic Valve Replacement

OBJECTIVES In the present study, the anatomy of the aortic root was assessed noninvasively with multislice computed tomography (MSCT). BACKGROUND Transcatheter aortic valve replacement has been proposed as an alternative to surgery in high-risk patients with severe aortic stenosis. For this procedure, detailed knowledge of aortic annulus diameters and the relation between the annulus and the coronary arteries is needed. METHODS In 169 patients (111 men, age 54 +/- 11 years), a 64-slice MSCT scan was performed for evaluation of coronary artery disease. Of these, 150 patients had no or mild aortic stenosis, and 19 patients had moderate to severe aortic stenosis. Reconstructed coronal and sagittal views were used for assessment of the aortic annulus diameter in 2 directions. In addition, the distance between the annulus and the ostium of the right and left coronary arteries and the length of the coronary leaflets were assessed. The LV outflow tract and interventricular septum were analyzed on the single oblique sagittal view at end-diastole. RESULTS The diameter of the aortic annulus was 26.3 +/- 2.8 mm on the coronal view, and 23.5 +/- 2.7 mm on the sagittal view. Mean difference between the 2 diameters was 2.9 +/- 1.8 mm, indicating an oval shape of the aortic annulus. Mean distance between the aortic annulus and the ostium of the right coronary artery was 17.2 +/- 3.3 mm, and mean distance between the annulus and the ostium of the left coronary artery was 14.4 +/- 2.9 mm. In 82 patients (49%), the length of the left coronary leaflet exceeded the distance between the annulus and the ostium of the left coronary artery. There were no significant differences in the diameter of annulus, diameter of sinus of Valsalva, or the distance between the annulus, left coronary leaflet, and the ostium of the left coronary artery, between the patient with and without severe aortic stenosis. CONCLUSIONS The MSCT can provide detailed information on the shape of the aortic annulus and the relation between the annulus and the ostia of the coronary arteries. Thereby, MSCT may be helpful for avoiding paravalvular leakage and coronary occlusion and may facilitate the selection of candidates for transcatheter aortic valve replacement.

Probability of Cancer in Pulmonary Nodules Detected on First Screening CT

BACKGROUND Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up. METHODS We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer. RESULTS In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set. CONCLUSIONS Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; ClinicalTrials.gov number, NCT00751660.).

Percutaneous Transvenous Mitral Annuloplasty Initial Human Experience With Device Implantation in the Coronary Sinus

Background— Mitral annuloplasty is the most common surgical procedure performed for ischemic mitral regurgitation (MR). Surgical mitral annuloplasty is limited by morbidity, mortality, and MR recurrence. We evaluated the safety and feasibility of a transvenous catheter-delivered implantable device to provide a percutaneous alternative to surgical mitral annuloplasty. Methods and Results— Five patients with chronic ischemic MR underwent percutaneous transvenous implantation of an annuloplasty device in the coronary sinus. Implantation was successful in 4 patients. Baseline MR in the entire group was grade 3.0±0.7 and was reduced to grade 1.6±1.1 at the last postimplantation visit when the device was intact or the last postprocedural visit in the patient in whom the device was not successfully implanted. Separation of the bridge section of the device occurred in 3 of 4 implanted devices and was detected at 28 to 81 days after implantation. There were no postprocedural device-related complications. Conclusions— Percutaneous implantation of a device intended to remodel the mitral annulus is feasible. Initial experience suggests a possible favorable effect on MR. Percutaneous transvenous mitral annuloplasty warrants further evaluation as a less invasive alternative to surgical annuloplasty.

Progressive damage on high resolution computed tomography despite stable lung function in cystic fibrosis

For effective clinical management of cystic fibrosis (CF) lung disease it is important to closely monitor the start and progression of lung damage. The aim of this study was to investigate the ability of high-resolution computed tomography (HRCT) scoring systems and pulmonary function tests (PFT) to detect changes in lung disease. CF children (n=48) had two HRCT scans in combination with two PFT 2 yrs apart. Their scans were scored using five scoring systems (Castile, Brody, Helbich, Santamaria and Bhalla). “Sensitivity” was defined as the ability to detect disease progression. In this group of children, HRCT scores worsened. PFT remained unchanged or improved. Of the HRCT parameters, mucous plugging and the severity, extent and peripheral extension of bronchiectasis worsened significantly. Relationships between changes in HRCT scores and PFT were weak. Substantial structural lung damage was evident in some children who had normal lung function. These data show that high-resolution computed tomography is more sensitive than pulmonary function tests in the detection of early and progressive lung disease, and suggest that high-resolution computed tomography may be useful in the follow up of cystic fibrosis children and as an outcome measure in studies that aim to reduce lung damage.

A Prospective Evaluation of Dose Reduction and Image Quality in Chest CT Using Adaptive Statistical Iterative Reconstruction

OBJECTIVE The purpose of this study was to compare the subjective image quality, image noise, and radiation dose of chest CT images reconstructed with a 30% blend of iterative reconstruction and 70% conventional filtered back projection (FBP) with those of images generated with 100% FBP. SUBJECTS AND METHODS Clinically indicated chest CT examinations of 292 consecutively registered patients were prospectively alternately assigned to two scanners on which different reconstruction techniques were used: adaptive statistical iterative reconstruction (ASIR) blended with FBP and 100% FBP. Both acquisitions were performed with dose modulation (noise index, 25 for ASIR and 21 for FBP). Patient demographics and habitus were recorded. Two radiologists blinded to the reconstruction algorithm independently scored subjective image quality on a 3-point Likert scale and measured image noise and radiation dose. RESULTS Compared with FBP images, ASIR images had significantly lower subjective image quality (p = 0.01), less image noise (p = 0.02), and less radiation dose (p < 0.0001). The CT dose index of the ASIR cohort (11.3 ± 51) was significantly lower than that of the 100% FBP cohort (15.4 ± 6.3) (p < 0.0001). Interobserver agreement on subjective image quality was excellent for both ASIR and FBP (Cronbach α, 0.92, p < 0.0001; Cronbach α, 0.85, p < 0.0001). CONCLUSION In clinically indicated chest CT examinations, ASIR images had better image quality and less image noise at a lower radiation dose than images acquired with a conventional FBP reconstruction algorithm.

Role of multislice computed tomography in transcatheter aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) required precise knowledge of the anatomic dimensions and physical characteristics of the aortic valve, annulus, and aortic root. Most groups currently use angiography, transthoracic echocardiography (TTE), or transesophageal echocardiography (TEE) to assess aortic annulus dimensions and anatomy. However, multislice computed tomography (MSCT) may allow more detailed 3-dimensional assessment of the aortic root. Twenty-six patients referred for TAVR underwent MSCT. Scans were also obtained for 18 patients after TAVR. All patients underwent pre- and postprocedural aortic root angiography, TTE, and TEE. Mean differences in measured aortic annular diameters were 1.1 mm (95% confidence interval 0.5, 1.8) for calibrated angiography and TTE, -0.9 mm (95% confidence interval -1.7, -0.1 mm) for TTE and TEE, -0.3 mm (95% confidence interval -1.1, 0.6 mm) for MSCT (sagittal) and TTE, and -1.2 mm (95% confidence interval -2.2, -0.2 mm) for MSCT (sagittal) and TEE. Coronal systolic measurements using MSCT, which corresponded to angiographic orientation, were 3.2 mm (1st and 3rd quartiles 2.6, 3.9) larger than sagittal systolic measurements, which were in the same anatomic plane as standard TTE and TEE views. There was no significant association between either shape of the aortic annulus or amount of aortic valve calcium and development of perivalvular aortic regurgitation. After TAVR, the prosthesis extended to or beyond the inferior border of the left main ostium in 9 of 18 patients (50%), and in 11 patients (61%), valvular calcium was <5 mm from the left main ostium. In conclusion, MSCT identified that the aortic annulus was commonly eccentric and often oval. This may in part explain the small, but clinically insignificant, differences in measured aortic annular diameters with other imaging modalities. MSCT after TAVR showed close proximity of both the prosthesis and displaced valvular calcium to the left main ostium in most patients. Neither eccentricity nor calcific deposits appeared to contribute significantly to severity of paravalvular regurgitation after TAVR.

Airway Wall Thickness Assessed Using Computed Tomography and Optical Coherence Tomography

RATIONALE Computed tomography (CT) has been shown to reliably measure the airway wall dimensions of medium to large airways. Optical coherence tomography (OCT) is a promising new micron-scale resolution imaging technique that can image small airways 2 mm in diameter or less. OBJECTIVES To correlate OCT measurements of airway dimensions with measurements assessed using CT scans and lung function. METHODS Forty-four current and former smokers received spirometry, CT scans, and OCT imaging at the time of bronchoscopy. Specific bronchial segments were identified and measured using the OCT images and three-dimensional reconstructions of the bronchial tree using CT. MEASUREMENTS AND MAIN RESULTS There was a strong correlation between CT and OCT measurements of lumen and wall area (r = 0.84, P < 0.001, and r = 0.89, P < 0.001, respectively). Compared with CT, OCT measurements were lower for both lumen and wall area by 31 and 66%, respectively. The correlation between FEV(1)% predicted and CT and OCT measured wall area (as percentage of the total area) of fifth-generation airways was very strong (r = -0.79, r = -0.75), but the slope of the relationship was much steeper using OCT than using CT (y = -0.33x + 82, y = -0.1x + 78), indicating greater sensitivity of OCT in detecting changes in wall measurements that relate to FEV(1). CONCLUSIONS OCT can be used to measure airway wall dimensions. OCT may be more sensitive at detecting small airway wall changes that lead to FEV(1) changes in individuals with obstructive airway disease.

Reduced Iodine Load at CT Pulmonary Angiography with Dual-Energy Monochromatic Imaging: Comparison with Standard CT Pulmonary Angiography—A Prospective Randomized Trial

PURPOSE To compare quantitative and subjective image quality and radiation dose between standard computed tomographic (CT) pulmonary angiography (CTPA) and CTPA with a dual-energy technique with reduced iodine load. MATERIALS AND METHODS This prospective study was approved by the institutional review board and each participant provided informed consent. Ninety-four patients (59% male; mean age ± standard deviation, 62 years ± 15) were randomized to one of two protocols: standard CTPA (100-120 kVp) with standard contrast medium injection (n = 46) and dual-energy CTPA (image reconstruction at 50 keV) with the same injection volume as in the standard protocol but composed of contrast medium and saline in a 1:1 fashion, resulting in 50% reduction in iodine load (n = 48). Signal intensity and noise in three central and two segmental pulmonary arteries were measured; signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. A five-point scale was used to subjectively evaluate vascular enhancement and image noise. The proportion of diagnostic (score, ≥ 3) studies and the interreader agreement regarding the dichotomized diagnostic versus nondiagnostic scale were compared between the two groups. RESULTS Compared with standard CTPA, dual-energy CTPA demonstrated higher signal intensity in all pulmonary arteries (all P < .01), inferior noise only in segmental arteries (P < .05), higher SNR and CNR (both P < .05), and compatible effective dose (P > .05). The five-point score was higher in the standard CTPA protocol (P < .05). The interreader agreement regarding the dichotomized diagnostic versus nondiagnostic scale was similar (P > .05) between the two groups. CONCLUSION Dual-energy CTPA with image reconstruction at 50 keV allows a significant reduction in iodine load while improving intravascular signal intensity, maintaining SNR and with comparable radiation dose.

New and Current Clinical Imaging Techniques to Study Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by both small airway and parenchymal abnormalities. There is increasing evidence to suggest that these two morphologic phenotypes, although related, may have different clinical presentations, prognosis, and therapeutic responses to medications. With the advent of novel imaging modalities, it is now possible to evaluate these two morphologic phenotypes in large clinical studies using noninvasive or minimally invasive methods such as computed tomography (CT), magnetic resonance imaging (MRI), and optical coherence tomography (OCT). In this article, we provide an overview of these imaging modalities in the context of COPD and discuss their strengths as well as their limitations for providing quantitative COPD phenotypes.