The effects of iterative reconstruction and kernel selection on quantitative computed tomography measures of lung density.

PURPOSE: To determine the effects of iterative reconstruction (IR) and high-frequency kernels on quantitative computed tomography (qCT) density measures at reduced X-ray dose. MATERIALS AND METHODS: The COPDGene 2 Phantom (CTP 698, The Phantom Laboratory, Salem, NY) with four embedded lung mimicking foam densities (12lb, 20lb, and 4lb), as well as water, air, and acrylic reference inserts, was imaged using a GE 64 slice CT750 HD scanner in helical mode with four current-time products ranging from 12 to 100 mAs. The raw acquired data were reconstructed using standard (STD - low frequency) and Bone (high frequency) kernels with filtered back projection (FBP), 100% ASiR, and Veo reconstruction algorithms. The reference density inserts were manually segmented using Slicer3D (www.slicer.org), and the mean, standard deviation, and histograms of the segmented regions were generated using Fiji (http://fiji.sc/Fiji) for each reconstruction. Measurements of threshold values placed on the cumulative frequency distribution of voxels determined by these measured histograms at 5%, PD5phant , and 15%, PD15phant , (analogous to the relative area below -950 HU (RA-950) and percent density 15 (PD15) in human lung emphysema quantification, respectively), were also performed. RESULTS: The use of high-resolution kernels in conjunction with ASiR and Veo did not significantly affect the mean Hounsfield units (HU) of each of the density standards (< 4 HU deviation) and current-time products within the phantom when compared with the STD+FBP reconstruction conventionally used in clinical applications. A truncation of the scanner reported HU values at -1024 that shifts the mean toward more positive values was found to cause a systematic error in lower attenuating regions. Use of IR drove convergence toward the mean of measured histograms (~100-137% increase in the number measured voxels at the mean of the histogram), while the combination of Bone+ASiR preserved the standard deviation of HU values about the mean compared to STD+FBP, with the added effect of improved spatial resolution and accuracy in airway measures. PD5phant and PD15phant were most similar between the Bone+ASiR and STD+FBP in all regions except those affected by the -1024 truncation artifact. CONCLUSIONS: Extension of the scanner reportable HU values below the present limit of -1024 will mitigate discrepancies found in qCT lung densitometry in low-density regions. The density histogram became more sharply peaked, and standard deviation was reduced for IR, directly effecting density thresholds, PD5phant and PD15phant, placed on the cumulative frequency distribution of each region in the phantom, which serve as analogs to RA-950 and PD15 typically used in lung density quantitation. The combination of high-frequency kernels (Bone) with ASiR mitigates this effect and preserves density measures derived from the image histogram. Moreover, previous studies have shown improved accuracy of qCT airway measures of wall thickness (WT) and wall area percentage (WA%) when using high-frequency kernels in combination with ASiR to better represent airway walls. The results therefore suggest an IR approach for accurate assessment of airway and parenchymal density measures in the lungs.

Standardizing CT lung density measure across scanner manufacturers.

PURPOSE: Computed Tomography (CT) imaging of the lung, reported in Hounsfield Units (HU), can be parameterized as a quantitative image biomarker for the diagnosis and monitoring of lung density changes due to emphysema, a type of chronic obstructive pulmonary disease (COPD). CT lung density metrics are global measurements based on lung CT number histograms, and are typically a quantity specifying either the percentage of voxels with CT numbers below a threshold, or a single CT number below which a fixed relative lung volume, nth percentile, falls. To reduce variability in the density metrics specified by CT attenuation, the Quantitative Imaging Biomarkers Alliance (QIBA) Lung Density Committee has organized efforts to conduct phantom studies in a variety of scanner models to establish a baseline for assessing the variations in patient studies that can be attributed to scanner calibration and measurement uncertainty. METHODS: Data were obtained from a phantom study on CT scanners from four manufacturers with several protocols at various tube potential voltage (kVp) and exposure settings. Free from biological variation, these phantom studies provide an assessment of the accuracy and precision of the density metrics across platforms solely due to machine calibration and uncertainty of the reference materials. The phantom used in this study has three foam density references in the lung density region, which, after calibration against a suite of Standard Reference Materials (SRM) foams with certified physical density, establishes a HU-electron density relationship for each machine-protocol. We devised a 5-step calibration procedure combined with a simplified physical model that enabled the standardization of the CT numbers reported across a total of 22 scanner-protocol settings to a single energy (chosen at 80 keV). A standard deviation was calculated for overall CT numbers for each density, as well as by scanner and other variables, as a measure of the variability, before and after the standardization. In addition, a linear mixed-effects model was used to assess the heterogeneity across scanners, and the 95% confidence interval of the mean CT number was evaluated before and after the standardization. RESULTS: We show that after applying the standardization procedures to the phantom data, the instrumental reproducibility of the CT density measurement of the reference foams improved by more than 65%, as measured by the standard deviation of the overall mean CT number. Using the lung foam that did not participate in the calibration as a test case, a mixed effects model analysis shows that the 95% confidence intervals are [-862.0 HU, -851.3 HU] before standardization, and [-859.0 HU, -853.7 HU] after standardization to 80 keV. This is in general agreement with the expected CT number value at 80 keV of -855.9 HU with 95% CI of [-857.4 HU, -854.5 HU] based on the calibration and the uncertainty in the SRM certified density. CONCLUSIONS: This study provides a quantitative assessment of the variations expected in CT lung density measures attributed to non-biological sources such as scanner calibration and scanner x-ray spectrum and filtration. By removing scanner-protocol dependence from the measured CT numbers, higher accuracy and reproducibility of quantitative CT measures were attainable. The standardization procedures developed in study may be explored for possible application in CT lung density clinical data.

Normalizing computed tomography data reconstructed with different filter kernels: effect on emphysema quantification.

OBJECTIVES: To propose and evaluate a method to reduce variability in emphysema quantification among different computed tomography (CT) reconstructions by normalizing CT data reconstructed with varying kernels. METHODS: We included 369 subjects from the COPDGene study. For each subject, spirometry and a chest CT reconstructed with two kernels were obtained using two different scanners. Normalization was performed by frequency band decomposition with hierarchical unsharp masking to standardize the energy in each band to a reference value. Emphysema scores (ES), the percentage of lung voxels below -950 HU, were computed before and after normalization. Bland-Altman analysis and correlation between ES and spirometry before and after normalization were compared. Two mixed cohorts, containing data from all scanners and kernels, were created to simulate heterogeneous acquisition parameters. RESULTS: The average difference in ES between kernels decreased for the scans obtained with both scanners after normalization (7.7 ± 2.7 to 0.3 ± 0.7; 7.2 ± 3.8 to -0.1 ± 0.5). Correlation coefficients between ES and FEV1, and FEV1/FVC increased significantly for the mixed cohorts. CONCLUSIONS: Normalization of chest CT data reduces variation in emphysema quantification due to reconstruction filters and improves correlation between ES and spirometry. KEY POINTS: • Emphysema quantification is sensitive to the reconstruction kernel used. • Normalization allows comparison of emphysema quantification from images reconstructed with varying kernels. • Normalization allows comparison of emphysema quantification obtained with scanners from different manufacturers. • Normalization improves correlation of emphysema quantification with spirometry. • Normalization can be used to compare data from different studies and centers.

Paired inspiratory-expiratory chest CT scans to assess for small airways disease in COPD.

BACKGROUND: Gas trapping quantified on chest CT scans has been proposed as a surrogate for small airway disease in COPD. We sought to determine if measurements using paired inspiratory and expiratory CT scans may be better able to separate gas trapping due to emphysema from gas trapping due to small airway disease. METHODS: Smokers with and without COPD from the COPDGene Study underwent inspiratory and expiratory chest CT scans. Emphysema was quantified by the percent of lung with attenuation < -950HU on inspiratory CT. Four gas trapping measures were defined: (1) Exp(-856), the percent of lung < -856HU on expiratory imaging; (2) E/I MLA, the ratio of expiratory to inspiratory mean lung attenuation; (3) RVC(856-950), the difference between expiratory and inspiratory lung volumes with attenuation between -856 and -950 HU; and (4) Residuals from the regression of Exp(-856) on percent emphysema. RESULTS: In 8517 subjects with complete data, Exp(-856) was highly correlated with emphysema. The measures based on paired inspiratory and expiratory CT scans were less strongly correlated with emphysema. Exp(-856), E/I MLA and RVC(856-950) were predictive of spirometry, exercise capacity and quality of life in all subjects and in subjects without emphysema. In subjects with severe emphysema, E/I MLA and RVC(856-950) showed the highest correlations with clinical variables. CONCLUSIONS: Quantitative measures based on paired inspiratory and expiratory chest CT scans can be used as markers of small airway disease in smokers with and without COPD, but this will require that future studies acquire both inspiratory and expiratory CT scans.

Normalized CT dose index of the CT scanners used in the National Lung Screening Trial.

OBJECTIVE: The National Lung Screening Trial includes 33 participating institutions that performed 75,133 lung cancer screening CT examinations for 26,724 subjects during 2002-2007. For trial quality assurance reasons, CT radiation dose measurement data were collected from all MDCT scanners used in the trial. MATERIALS AND METHODS: A total of 247 measurements on 96 MDCT scanners were collected using a standard CT dose index (CTDI) measurement protocol. The scan parameters used in the measurements (tube voltage, milliampere-seconds [mAs], and detector-channel configuration) were set according to trial protocol for average size subjects. The normalized weighted CT dose index (CTDI(w)) (computed as CTDI(w)/mAs) obtained from each trial-participating scanner was tabulated. RESULTS: We found a statistically significant difference in normalized CT dose index among CT scanner manufacturers, likely as a result of design differences, such as filtration, bow-tie design, and geometry. Our findings also indicated a statistically significant difference in normalized CT dose index among CT scanner models from the same manufacturer (e.g., GE Healthcare, Siemens Healthcare, and Philips Healthcare). We also found a statistically significant difference in normalized CT dose index among all models and all manufacturers; furthermore, we found a statistically significant difference in normalized CT dose index among CT scanners from all manufacturers when we compared scanners with four or eight data channels to those with 16, 32, or 64 channels, suggesting that more complex scanners have improved dose efficiency. CONCLUSION: Average normalized CT dose index values varied by a factor of almost two for all scanners from all manufacturers. This study was focused on machine-specific normalized CT dose index; patient dose and image quality were not addressed.

Initial evaluation of coronary images from 320-detector row computed tomography.

PURPOSE: To evaluate image quality and contrast opacification from coronary images acquired from 320-detector row computed tomography (CT). Patient dose is estimated for prospective and retrospective ECG-gating; initial correlation between 320-slice CT and coronary catheterization is illustrated. METHODS: Retrospective image evaluation from forty consecutive patients included subjective assessment of image quality and contrast opacification (80 ml iopamidol 370 mg I/ml followed by 40 ml saline). Region of interest opacification measurements at the ostium and at 2.5 mm diameter were used to determine the gradient of contrast opacification (defined as the proximal minus distal HU measurements) in coronary arteries imaged in a single heartbeat. Estimated effective dose was compared for prospective versus retrospective ECG-gating, two body mass index categories (30 kg/m(2) cutoff), and single versus two heartbeat acquisition. When available, CT findings were correlated with those from coronary catheterization. RESULTS: Over 89% of arterial segments (15 segment model) had excellent image quality. The most common reason for image degradation was cardiac motion. One segment in one patient was considered unevaluable. Contrast opacification was almost universally considered excellent. The mean Hounsfield units (HU) was greater than 350; the coronary contrast opacification gradient was 30-50 HU. Patient doses were greater for retrospective ECG-gating, larger patients, and those imaged with two heartbeats. For the most common (n=25) protocol (120 kV, 400 mA, prospective ECG-gating, 60-100% phase window, 16 cm craniocaudal coverage, single heartbeat), the mean dose was 6.8+/-1.4 mSv. All CT findings were confirmed in the four patients who underwent coronary catheterization. CONCLUSION: Initial 320-detector row coronary CT images have consistently excellent quality and iodinated contrast opacification. These patients were scanned with conservative protocols with respect to iodine load, prospective ECG-gating phase window, and craniocaudal coverage. Future work will focus on lowering contrast and radiation dose while maintaining image quality.

Signal detection in power-law noise: effect of spectrum exponents.

Many natural backgrounds have approximately isotropic power spectra of the power-law form, P(f)=K/f(beta), where f is radial frequency. For natural scenes and mammograms, the values of the exponent, beta, range from 1.5 to 3.5. The ideal observer model predicts that for signals with certain properties and backgrounds that can be treated as random noise, a plot of log (contrast threshold) versus log (signal size) will be linear with slope, m, given by: m=(beta-2)/2. This plot is referred to as a contrast-detail (CD) diagram. It is interesting that this predicts a detection threshold that is independent of signal size for beta equal to 2. We present two-alternative forced-choice (2AFC) detection results for human and channelized model observers of a simple signal in filtered noise with exponents from 1.5 to 3.5. The CD diagram results are in good agreement with the prediction of this equation.

Reduced-dose CT: effect on reader evaluation in detection of pulmonary embolism.

OBJECTIVE: The purpose of this study was to evaluate the effect of reduction in radiation dose on CT detection of pulmonary embolism. SUBJECTS AND METHODS: Emergency department patients were evaluated for pulmonary embolism with standard and simulated reduced-dose CT angiography. Simulated lower-dose CT angiograms obtained at 90, 45, 22, and 10 mAs(eff) were reconstructed by mathematical addition of noise to the standard dose (180 mAs(eff)) data from the images of 18 patients with and 20 patients without pulmonary embolism. Four radiologists blinded to the study parameters separately interpreted each CT angiogram. Dose trends for subjective measures (diagnostic certainty, image quality, and perceived technical limitations) were evaluated, test characteristics for the detection of pulmonary embolism were computed, and clot burden was measured. RESULTS: Readers indicated significant reductions in diagnostic certainty (p < 0.02) and image quality (p < 0.02) and an increase in perceived technical limitations (p < 0.01) as the simulated radiation dose was decreased. These subjective measures also showed significant adverse dose trends when the mAs(eff) was reduced (p < 0.001). At reduced radiation doses, the sensitivity and positive predictive value for detection of pulmonary embolism diminished significantly. The sensitivity was 0.94 (lower bound of 0.95 CI, 0.92); specificity, 0.99 (lower bound of 0.95 CI, 0.98); positive predictive value, 0.95 (lower bound of 0.95 CI, 0.92); and negative predictive value, 0.99 (lower bound of 0.95 CI, 0.97). All patients had a low to moderate clot burden. CONCLUSION: Reduction in dose for CT angiography in the detection of pulmonary embolism has a significant adverse effect on readers' subjective assessment of diagnostic confidence and image quality. Detection of pulmonary embolism also decreases as the tube current dose is reduced.

Description and implementation of a quality control program in an imaging-based clinical trial.

RATIONALE AND OBJECTIVES: The American College of Radiology Imaging Network is participating in the National Lung Screening Trial, a large, multicenter, randomized controlled trial, comparing multidetector helical computed tomography (MDCT) versus chest radiography (CXR) in screening for lung cancer. Because the threshold for detection of disease is an inherent function of image quality, and consistent image quality is necessary to track changes in suspicious findings, our purpose was to develop an image quality control (QC) program across all clinical sites for both modalities. MATERIALS AND METHODS: The primary goals of the QC program include standardization of imaging protocols, certification of imaging equipment, and ongoing, periodic evaluation of the equipment calibration and image quality. Minimum standards for equipment and standardized cross-platform acquisition protocols are achieved via radiologist and physicist attestation forms and web-distributed technique charts, respectively. Imaging equipment performance standards are implemented through an initial machine certification process that includes equipment calibration. Ongoing assessment of equipment performance and calibration, as well as adherence to established imaging protocols. is accomplished via periodic submission of calibration records and phantom images. Participant-specific image acquisition parameters are entered into a web-based centralized database and variations from established protocols are automatically flagged for review. Participant radiation dose can be estimated from the image acquisition parameters applied to the imaging equipment calibration measurements. A radiologist visual review committee also evaluates participant images for diagnostic quality. Data are collected from 23 independent centers, representing 14 models of MDCT scanners from four manufacturers, and CXR systems that include film-screen, computed radiography, and direct digital radiography systems. RESULTS: Widespread imaging protocol variation in extant clinical practice-as well as variability in equipment technology, image acquisition parameters, manufacturer terminology, and user interface-have required careful standardization as a prerequisite to trial participation and ongoing image QC. Acceptable ranges for image acquisition parameters have been refined to accommodate continuously evolving equipment platforms and the scope of participant size and body habitus. CONCLUSION: Standardization of imaging protocols is a critical component of image-based clinical trials, predicated on ongoing dialogue between sites and a centralized review committee.

Lowering the thyroid dose in screening examinations of the cervical spine.

The first objective of this study was to test the hypothesis that a lower-dose (14.1 mGy thyroid dose) protocol for helical computed tomography (CT) of the entire cervical spine demonstrates equivalent technical adequacy and diagnostic accuracy as the standard-dose protocol (26.0 mGy thyroid dose) used at our institution. The second objective was to estimate the excess thyroid cancer mortality for three cervical spine screening protocols. Eight patients underwent two helical CT acquisitions of the entire cervical spine (standard and lower dose); from these acquisitions, a database of 128 randomized images (64 standard dose and 64 lower dose) was constructed. Three radiologists evaluated each of the 128 images for technical adequacy and, if the image was technically adequate, diagnostic accuracy. Historical data of excess thyroid cancer mortality stratified by age and sex were used to estimate the impact of lowering the thyroid dose in cervical spine screening. Estimates used a linear extrapolation of mortality data. The lower-dose protocol for helical CT of the entire cervical spine demonstrates equivalent technical adequacy and diagnostic accuracy as the standard protocol. The excess thyroid cancer mortality is a function of patient age and sex; for 25-year-old men, the excess mortality per 100,000 patients is 96.7 (standard-dose CT), 52.4 (lower-dose CT), and 6.7 (radiographs alone, 1.8 mGy thyroid dose). The equivalent technical adequacy and diagnostic accuracy of a lower-dose protocol for helical CT of the entire cervical spine support its implementation in routine screening. The excess thyroid mortality emphasizes the need to maintain an open dialogue with our referring clinicians with respect to the mechanism of injury, clinical findings, and radiation risks.

Evaluation of small (

OBJECTIVE: Our purpose was to determine whether thin overlapping reconstructions using MDCT improve the detection and characterization of small renal masses. MATERIALS AND METHODS: Thirty-seven patients were scanned with MDCT using 2.5-mm collimation. Nephrographic phase data were reconstructed in two ways: a standard protocol (5-mm section thickness, no overlap) and an experimental protocol (3-mm section thickness, 50% overlap). Masses were detected and classified into three groups: group 1, measuring less than 20 H on both protocols (classified as cysts on both); group 2, measuring 20 H or greater on standard protocol and less than 20 H on experimental protocol (classified as cysts using experimental protocol only); and group 3, measuring 20 H or greater on both protocols (not classified as cysts using either protocol). Masses 10 mm or larger in group 3 were evaluated further for enhancement. Statistically significant differences between protocols were assessed using an analysis of counts and proportions. RESULTS: Of 175 detected lesions, 29 (17%) were detected only with the experimental protocol; all but one were smaller than 5 mm. Using the experimental protocol, of 45 masses between 5 and 10 mm, the number of masses that could be characterized as cysts increased from 13 (29%) to 38 (84%). The overall number of indeterminate lesions was reduced from 101 (69%) of 146 lesions detected with the standard protocol to 86 (53%) of 161 lesions detected with the experimental protocol. CONCLUSION: Using MDCT and thin overlapping reconstructions, renal cysts as small as 5 mm can be diagnosed with more confidence than is possible with standard reconstructions, and the overall number of indeterminate renal masses is reduced.

Patient radiation dose at CT urography and conventional urography.

PURPOSE: To measure and compare patient radiation dose from computed tomographic (CT) urography and conventional urography and to compare these doses with dose estimates determined from phantom measurements. MATERIALS AND METHODS: Patient skin doses were determined by placing a thermoluminescent dosimeter (TLD) strip (six TLD chips) on the abdomen of eight patients examined with CT urography and 11 patients examined with conventional urography. CT urography group consisted of two women and six men (mean age, 55.5 years), and conventional urography group consisted of six women and five men (mean age, 58.9 years). CT urography protocol included three volumetric acquisitions of the abdomen and pelvis. Conventional urography protocol consisted of acquisition of several images involving full nephrotomography and oblique projections. Mean and SD of measured patient doses were compared with corresponding calculated doses and with dose measured on a Lucite pelvic-torso phantom. Correlation coefficient (R(2)) was calculated to compare measured and calculated skin doses for conventional urography examination, and two-tailed P value significance test was used to evaluate variation in effective dose with patient size. Radiation risk was calculated from effective dose estimates. RESULTS: Mean patient skin doses for CT urography measured with TLD strips and calculated from phantom data (CT dose index) were 56.3 mGy +/- 11.5 and 54.6 mGy +/- 4.1, respectively. Mean patient skin doses for conventional urography measured with TLD strips and calculated as entrance skin dose were 151 mGy +/- 90 and 145 mGy +/- 76, respectively. Correlation coefficient between measured and calculated skin doses for conventional urography examinations was 0.95. Mean effective dose estimates for CT urography and conventional urography were 14.8 mSv +/- 90.0 and 9.7 mSv +/- 3.0, respectively. Mean effective doses estimated for the pelvic-torso phantom were 15.9 mSv (CT urography) and 7.8 mSv (conventional urography). CONCLUSION: Standard protocol for CT urography led to higher mean effective dose, approximately 1.5 times the radiation risk for conventional urography. Patient dose estimates should be taken into consideration when imaging protocols are established for CT urography.

Assessment and validation of imaging methods and technologies.

In summary, the group identified many challenges and opportunities facing those wishing to conduct rigorous assessment and validation of imaging technologies. Specific needs and recommendations were outlined by the group. Overall, it was felt that the field has made great progress in the past several years, and that the future is promising.

Skin and thyroid dosimetry in cervical spine screening: two methods for evaluation and a comparison between a helical CT and radiographic trauma series.

OBJECTIVE: The first objective of this study was to test the hypothesis that estimates of radiation dose from an ionization chamber correspond to thermoluminescent dosimeter measurements in patients with suspected cervical spine injury. The second objective was to compare the radiation dose of a protocol using helical CT of the entire cervical spine with that of a protocol using radiography alone. SUBJECTS AND METHODS: Thermoluminescent dosimeter measurements of radiation dose to the skin over the thyroid were made in two patient groups: six patients evaluated with CT of the cervical spine and six patients evaluated with radiography. The skin dose for both groups was estimated with an ionization chamber, and the thermoluminescent dosimeter measurements and ionization chamber estimates of skin dose were compared for both groups. Using the ionization chamber, we estimated the radiation dose to the thyroid for all 12 patients. With these estimates, we computed the ratios of skin dose and thyroid dose (CT / radiography). RESULTS: Thermoluminescent dosimeter measurements correlated with ionization chamber estimates of skin dose in both patient groups. Using the ionization chamber estimates, we found that CT delivered 26.0 mGy to the thyroid. In the patients evaluated with radiography, the mean thyroid dose was 1.80 mGy (95% confidence interval, 1.05-2.55 mGy). Ionization chamber dose ratios (CT / radiography) for the skin and thyroid were 9.69 and 14.4 mGy, respectively. CONCLUSION: The correlation between the ionization chamber estimates and the thermoluminescent dosimeter measurements supports the use of ionization chamber estimates in future research. Although helical CT of the entire cervical spine is cost-effective in patients at high risk for fracture, the greater than 14-fold increase in the radiation dose to the thyroid emphasizes the importance of clinical stratification to identify patients at high risk for fracture and the judicious use of CT in patients with suspected cervical spine injury.