J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 5 5 e2 6 3
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofCardiovascularCT.com
Review Article
Iterative reconstruction in cardiac CT Christopher Naoum MBBS, Philipp Blanke MD, Jonathon Leipsic MD* Department of Medical Imaging and Division of Cardiology, St Paul’s Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6
article info
abstract
Article history:
Iterative reconstruction (IR) has the ability to reduce image noise in CT without compro-
Received 17 March 2015
mising diagnostic quality, which permits a significant reduction in effective radiation dose.
Received in revised form
This been increasingly integrated into clinical CT practice over the past 7 years and has
15 April 2015
been particularly important in the field of cardiac CT with multiple vendors introducing
Accepted 15 April 2015
cardiac CTecompatible IR algorithms. The following review will summarize the principles
Available online 21 April 2015
of IR algorithms, studies validating their noise- and dose-reducing abilities, and the specific applications of IR in cardiac CT.
Keywords:
ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved.
Iterative reconstruction Cardiac computed tomography Coronary computed tomography Radiation dose
1.
Introduction
Since its introduction into clinical medicine over 40 years ago, CT has undergone tremendous technical advancements, some of the most important ranging from the development of slip ring technology to multiple-row detectors and electrocardiography (ECG) synchronization. Iterative reconstruction (IR), although currently perceived as a new technology, has in fact been available since the early 1980s with widespread use in nuclear medicine imaging. The lack of sufficient computational processing capabilities had precluded its routine use in clinical CT until recently. With its reintroduction in 2008, a number of new IR algorithms have been developed and undergone successful integration into clinical practice over the past 7 years. Given the widespread adoption and rapid development of this technology, an understanding of the pertinent
principles of IR and its clinical applications is of importance for clinicians involved in cardiac CT practice. Accordingly, the present review will provide an overview of the principles of IR, currently available clinical versions, and advancements in the application of IR in the field of cardiac CT.
2. General principles of reconstruction algorithms 2.1.
Filtered back projection
Until recently, CT images were almost exclusively reconstructed with filtered back projection (FBP), largely because of the fact that FBP generates diagnostic images at a low level of computational complexity. FBP operates on a simplified model
Conflict of interest: Jonathon Leipsic serves on the speaker’s bureau for GE Healthcare and is a consultant for HeartFlow. The other authors report no conflict of interest. * Corresponding author. E-mail address: [email protected] (J. Leipsic). 1934-5925/$ e see front matter ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved. http://dx.doi.org/10.1016/j.jcct.2015.04.004
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whereby the x-ray beam assumes a pencil shape and the x-ray source is aligned in a parallel fashion to a linear x-ray detector array. For image generation, the x-ray source is rotated over a predetermined angle, allowing for intensities to be measured at the detector. These intensities are described as an integral function for a specific angle and the shift in the position of the x-ray tube. After this, the reconstruction process involves solving an integral equation by inversion or so-called “back projection.” Despite its ability to rapidly reconstruct images, FBP has a number of limitations. In particular, they include increased image noise (which is most pronounced with low tube current imaging), poor contrast resolution, and streak artifacts. This is primarily due to the inherent failure of the FBP algorithm to account for image noise that results from Poisson statistical variations in the number of photons across the imaging plane and leads to the inverse relationship between radiation dose and image noise. Until the recent introduction of IR, therefore, lowering image noise could only be achieved at the expense of increased radiation dose. Attempts at “image-based denoising” through smoothing algorithms and IR filters (convolution kernels) allow for noise reduction but result in a compromise in image fidelity and spatial resolution.
2.2.
IR algorithms
IR techniques attempt to localize and selectively remove image noise through more “true” IR. This is achieved through a process of modeling of the imaging acquisition process including fluctuations in photon statistics, the optics system, and other aspects of x-ray interactions to generate an expected data set, which is then compared to the acquired data set. The differences between the 2 are used to identify and remove noise, and the process is repeated multiple times until the updated data converges with or approximates the expected data to maximally optimize the image. The first IR algorithm used in CT was the algebraic reconstruction technique, which reconstructed images through an iterative algorithm solving for linear algebraic equations and was the method of IR used in the very first CT scanner.1 Subsequent upgrades of this algorithm were developed but limited by their computational complexity,2 leading to the rapid adoption of the simpler technique of FBP. With recent advancements in computational power, however, IR re-emerged with statistical algorithms appearing first. Statistical IR deals with noise due to fluctuations in photon statistics by assigning a relatively higher weighting to data with low statistical uncertainty (low noise) and lesser weighting to data with high statistical uncertainty (high noise). It operates in either the “raw data domain” with subsequent reconstruction using the “noisereduced” data or in the “image domain” after IR. More recently, IR algorithms that model for the physical 3-dimensional nature of the system optics (geometric modeling of the focal point of the x-ray tube and pixel detector) and the interaction of photons in the transmission between the x-ray tube, isocenter, and detector (physical modeling) have also been developed and are collectively referred to as model-based IR (MBIR).3 Current IR algorithms typically combine statistical modeling with MBIR.
3. Radiation dose and noise reduction using IR algorithms in cardiac CT Growing concern in the last decade over patient radiation exposure was intensified by the Protection I study, which reported a median effective dose of 11.2 mSv across 47 sites for retrospectively gated cardiac CT and, more importantly, average doses of >25 mSv in some of the participating sites.4 Accordingly, a number of dose-reduction strategies have emerged. The simplest form of dose reduction, tube current reduction, has been limited in its implementation owing to its inverse relationship to image noise. With IR, however, diagnostic images can be achieved at lower tube currents, as the IR process reduces noise compared to FBP and therefore compensates some of the increased noise that would occur with FBP if tube current were lowered. Hence, effective dose can be significantly decreased while maintaining acceptable levels of image noise. Many studies have evaluated noise and dose reduction with IR algorithms across multiple vendors. These studies may be summarized as demonstrating either (1) improved noise properties with IR compared to FBP when images from the same patients are reconstructed using both algorithms (intraindividual analysis) or (2) preserved subjective image quality and quantitative noise properties among patients undergoing IR image reconstruction with low radiation dose techniques (reduced tube current and/or potential) compared to FBP algorithms with standard dose techniques (interindividual analysis). Specific IR algorithms used in cardiac CT and studies validating their noise- and dose-reducing abilities are discussed in the following sections.
3.1.
General Electric
3.1.1.
Adaptive Statistical Iterative Reconstruction
Adaptive statistical iterative reconstruction (ASiR; GE Healthcare, Milwaukee, WI), introduced in 2008, was the first IR algorithm used in cardiac CT.5 It operates in the raw data domain using FBP data as a building block and photon statistics to convert the measured pixel value to an idealized pixel value. ASiR is regarded a hybrid IR algorithm in that it can be blended with traditional FBP (at 10% thresholds). Early validation using ASiR was promising with the ERASIR trial documenting the possibility of a 44% dose reduction (4.1 mSv vs 2.3 mSv) while maintaining comparable image quality and noise properties compared to full-dose FBP coronary CT angiography (CTA) among prospectively enrolled patients at 3 sites.6 The best low-dose cardiac CTA results were obtained when a level of 40% to 60% ASiR was combined with FBP.7 Retrospective analyses showed comparable results, with one study demonstrating a 24% dose reduction among patients undergoing coronary CTA with ASiR reconstruction compared to FBP despite no differences in signal intensity, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), or diagnostic quality.8 Gosling et al9 demonstrated that while coronary CTA with FBP reconstruction resulted in a similar dose to invasive coronary angiography (ICA) (5.4 mSv vs 6.3 mSv), there was a 54% dose reduction using ASiR reconstruction (2.5 mSv) (Fig. 1).
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3.1.2.
VEO
VEO is a more complex algorithm that incorporates extensive modeling of system optics (MBIR) in addition to the statistical modeling performed in ASiR. Both experimental and clinical studies have been reported. One study of 3 ex vivo human donor hearts imaged by CT showed significantly improved image quality and CNR and reduced noise among MBIR reconstructions compared to FBP and ASiR.10 MBIR was also associated with improved plaque assessment using automated software, particularly in segments with moderate and severe calcification.11 More recently, in a single-center study of 42 patients, MBIR reconstruction permitted an 82% dose reduction using an ultra-low-dose coronary CTA scan protocol (80e100 kVp; 150e210 mAs, MBIR) compared to standard coronary CTA (100e120 kVp; 450e700 mAs, 30% ASiR) while preserving diagnostic image quality and enhancing SNR in the proximal coronary vessels.12
3.1.3.
Adaptive Statistical Iterative Reconstruction-V
GE Healthcare’s latest IR algorithm, ASiR-V, differs from previous generations by de-emphasizing system optics modeling and using more advanced noise and object modeling as well as introducing physics modeling. Through a reduced focus on optics modeling, ASiR-V reconstructions can be generated in significantly less time. Relative differences in subjective image quality are demonstrated in Fig. 2; however, studies validating the clinical utility of ASiR-V in coronary CTA are still needed.
3.2.
Philips
3.2.1.
iDose4
257
Philips Healthcare (Best, the Netherlands) introduced “iDose4” in 2010, a unique IR algorithm that operates in both the raw and imaging data domains. Projection data is first analyzed to identify the noisiest measurements (poor SNR or low photon counts) by applying a model that includes photon statistics. Of importance, an iterative diffusion process is used that distinguishes noise from edges. This technique aims at preventing photon starvation artifacts (streaks, bias) before image creation. After this step, the noise is propagated to the image space but remains highly localized. Further structural modeling and dynamic model-based noise removal are applied iteratively in the image space to remove noise while preserving edges of true anatomic structures.13 Noise can be removed to varying levels depending on the need to image the heart at low dose vs improving image quality. iDose4 is particularly effective at generating images with reduced noise without creating the artificial appearance of images that has been typical of earlier generation IR techniques (Fig. 3).14 The effect of iDose4 in coronary CTA was studied in 200 consecutively referred patients sequentially assigned to FBP or IR. While achieving similar image quality, IR permitted a 39% dose reduction (2.8 1.4 mSv vs 4.6 3.0 mSv).15 Hou et al16 conducted a number of clinical studies validating iDose4. Among 109 patients undergoing ECG-gated helical 256-slice coronary CTA, IR performed with a 55% reduction in dose provided equivalent or improved coronary image quality
Fig. 1 e ASiR-V (GE Healthcare). Curved multiplanar reformats demonstrating the left anterior descending coronary artery with a coronary stent. Images are reconstructed with filtered back projection (A) and ASiR-V 50% (B) and 80% (C). ASiR, adaptive statistical iterative reconstruction. Images courtesy of Dr Ricardo Cury, Baptist Hospital, Miami.
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Fig. 2 e iDose4 and IMR (Phillips). Curved multiplanar images demonstrating a high-grade stenosis in the proximal left anterior descending coronary artery. Images are reconstructed using filtered back projection (A), iDose4 (B), and IMR (C). IMR, Iterative Model Reconstruction. Images courtesy of Philips Healthcare.
compared to FBP. The optimal level of iDose4 tube current reduction that could be achieved without compromising image quality was 63% in phantom and clinical studies using prospective ECG-gated 256-slice CTA.17,18 Improved image quality (CNR, visualization of distal vessels, and number of interpretable segments) and interobserver agreement were also shown in another study of 20 patients undergoing coronary CTA using iDose4 and FBP reconstruction.19
3.2.2.
Iterative Model Reconstruction
Iterative Model Reconstruction (IMR), a knowledge-based IR algorithm that significantly improves low-contrast resolution, was recently introduced. Clinical studies showed an additional improvement in subjective image quality and noise properties using IMR compared with both hybrid IR techniques and FBP among patients undergoing prospectively ECG-triggered coronary CTA performed at low tube voltage
(100 kVp) using a 256-slice scanner.20 IMR led to >80% intravascular noise reduction compared to FBP and improved image quality at 80% lower radiation exposure compared to standard techniques with FBP21 (Fig. 3).
3.3.
Siemens
3.3.1.
Iterative Reconstruction in Image Space
Iterative Reconstruction in Image space (IRIS) was released in 2008 by Siemens Healthcare (Forchheim, Germany).22 Unlike other IR algorithms, IRIS is based in the image domain. This means that an initial image is reconstructed from the acquired raw data. Subsequent repeated applications of the IR algorithm only use the image data (not the acquired raw data) to reduce image noise and enhance object contrast. In dose comparison studies, similar image quality was shown among 12 patients imaged with standard tube voltage
Fig. 3 e ADMIRE (Siemens). Curved multiplanar reformats demonstrating a proximal right coronary artery noncalcified plaque causing luminal stenosis reconstructed with filtered back projection (A) and ADMIRE (B). ADMIRE, Advanced Model Iterative Reconstruction. Images courtesy of Dr Stephan Achenbach and Dr Mohamed Marwan, Erlangen University, Erlangen.
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coronary CTA (120 kVp) and FBP and 12 matched patients imaged at lower tube voltage (80e100kVp) and IRIS reconstruction using a 62% dose reduction.23
3.3.2.
Sinogram Affirmed Iterative Reconstruction
Siemens subsequently introduced a raw data space IR algorithm in 2010, Sinogram Affirmed Iterative Reconstruction (SAFIRE), which operates in both the raw and image space domains. It uses FBP as a backbone and integrates a correction loop whereby a dynamic noise model is repeatedly applied to reduce image noise. A second correction occurs in the image space where noise is removed through statistical optimization based on knowledge of how the noise in the raw data is propagated to the image space.24 A number of strength levels are available (between 1 and 5) to allow for various degrees of blending IR reconstruction with FBP reconstruction, which influences the balance between noise reduction and image appearance.25 SAFIRE is a robust algorithm and is time efficient with 20 images reconstructed per second.26 Multiple studies have consistently validated the ability of SAFIRE to reduce image noise and therefore radiation dose. In a study of 60 patients that underwent standard coronary CTA with FBP followed by a second acquisition using 50% of initial tube current and reconstructed with SAFIRE, image quality and diagnostic accuracy using ICA as the reference standard was maintained despite a 52% reduction in radiation dose exposure.27 SAFIRE also led to improved image quality in coronary CTA acquisitions using tube currents reduced by as much as 80%.28 Reduced radiation dose was also achieved in a combined water phantom and clinical study of 49 patients using retrospective ECG gating with a dual-source CT (DSCT) scanner and SAFIRE reconstruction without compromising image quality.29 Finally, even the feasibility of very low-dose coronary CTA has also been demonstrated. In 50 patients that underwent prospectively ECG-triggered DSCT (0.66 0.05 mSv), subjective image quality and noise properties were significantly better with SAFIRE compared to FBP reconstructions.30
3.3.3.
Advanced Model Iterative Reconstruction
The latest Siemens IR algorithm, Advanced Model Iterative Reconstruction (ADMIRE), builds on SAFIRE but uses more advanced modeling to improve image resolution and edge detection in addition to noise reduction. Recently, reduced image noise and improved image quality compared to FBP were shown when low-dose coronary CTA (0.3 0.03 mSv) was performed using ADMIRE reconstructions31 (Fig. 3).
3.4.
Toshiba
3.4.1.
Adaptive Iterative Dose Reduction (AIDR/AIDR 3D)
The first algorithm introduced by Toshiba Medical Systems (Otawara, Japan), Adaptive Iterative Dose Reduction (AIDR) operated primarily in the image domain. The original highnoise images experience multiple iterative loops to achieve the appropriate noise levels.32,33 This technique has been replaced by a new technique using a 3-dimensional processing algorithm (AIDR-3D).34 This allows for a morphing of this reconstruction algorithm from the image domain to the raw data space. Both quantum and electrical noise from the x-ray photons and the CT system, respectively, are modeled.
259
Moreover, statistical noise and scanner-specific geometric models are used to help reduce image noise (Fig. 4). Improved image quality with reduced radiation dose has been demonstrated with AIDR-3D compared to both AIDR and FBP in a total of 942 patients undergoing coronary CTA using 1 of the 3 reconstruction algorithms.35 Studies with 50% simulated dose reduction and AIDR-3D reconstruction have shown image quality that was at least comparable to standard coronary CTA imaging with FBP.36
4.
Effect on plaque assessment
IR changes image appearance compared to standard FBP reconstructions (to various degrees depending on the specific IR method that is applied). There is concern that this may affect the ability of CT to identify stenoses and characterize plaque in the coronary arteries. Multiple studies have therefore evaluated the effect of IR algorithms on the accuracy of plaque stenosis and composition assessment. Preserved diagnostic accuracy and subjective image quality were demonstrated in 60 patients who prospectively underwent 2 coronary CTA scans before ICA, which was used as the reference standard. The first scan was performed using standard radiation dose settings and FBP reconstruction and the second using 50% tube current-time reduction and SAFIRE reconstruction.27 Similar results were also observed at ultralow CTA dose (0.58 0.17 mSv) using SAFIRE combined with ECG-triggered high-pitch spiral acquisition.37 Comparable diagnostic accuracy was also shown between FBP reconstruction and SAFIRE reconstruction using only 50% of the projections by discarding data from one of the tube-detector systems (therefore simulating half radiation dose) in 65 consecutive patients who underwent DSCT.26 In one study of 50 patients undergoing coronary CTA, the best diagnostic performance (not statistically significant) was observed with strength factor 3, which was 95% accurate for diagnosing a >50% stenosis using ICA as the reference standard. Of interest, among 126 of 593 segments (in 36 of 50 patients) with significant stenosis (>50% on ICA), appropriate reclassification from false positive to true negative on coronary CTA occurred in 9 segments with severe calcification.38 Studies evaluating the effect of IR algorithms on plaque volume and composition assessment have generally demonstrated minimal effect on quantified volume but a tendency toward lower percentage of high-attenuation plaque compared to FBP. In one study of 9 ex vivo coronary arteries, CT generally overestimated plaque burden compared to intravascular ultrasonography (10 10%), whereas there was no difference between FBP, ASiR, or MBIR reconstructions.39 Similarly, ASiR did not result in a significant difference in plaque volume by automated plaque assessment software among 29 consecutive patients with 50 lesions but did result in a tendency to more soft and intermediate plaque components compared to FBP. When stratified by Hounsfield Units (HU), the percentage of plaque volume with attenuation values between 400 HU and 500 HU decreased significantly using ASiR.40 In a coronary CTA study of 63 patients with 55 coronary plaques, iDose4 (at 3 different levels) had no effect on plaque volume, composition, or luminal area assessment
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Fig. 4 e AIDR-3D (Toshiba). Axial cardiac CTA images demonstrating significantly less noise with AIDR-3D reconstruction (A) with noise value of 37.1 within the region of interest as compared to FBP with a noise value of 102.7. This was realized while maintaining image signal 829.8 vs 831.4. (B) despite similar signal intensity. Curved multiplanar reformats of the right coronary artery are demonstrated for AIDR-3D (C) and FBP (D) with the insets highlighting differences in coronary artery image quality between reconstruction algorithms. AIDR, Adaptive Iterative Dose Reduction; CTA, CT angiography; FBP, filtered back projection; HU, Hounsfield units. Images courtesy of Dr Marcus Chen, NIH, Bethesda.
compared to FBP.41 In a recent study of 3 ex vivo hearts, 173 cross-sectional coronary segments were coregistered between 3 different reconstruction methods (FBP, ASiR, MBIR) and histology. MBIR was more accurate for the detection of histologically verified lipid core plaque compared to both ASiR and FBP.42 In summary, there are still limited data regarding the ability of IR to improve coronary plaque detection and characterization, but there is justified hope for improved coronary plaque characterization in the future.
5. Applications of IR in specific patient populations Although dose reduction is the primary goal of IR in cardiac CT, there are some patients where noise properties are
unacceptable even if higher tube currents are used, for example, patients with elevated body mass index (BMI) and patients with extensive coronary artery calcification or prior coronary stenting. The ability to reduce noise with IR offers an opportunity to image patients that previously posed a significant problem for coronary CTA.
5.1.
Elevated BMI
Studies primarily evaluating the utility of IR in improving image quality of coronary CTA among patients with elevated BMI have demonstrated positive results. ASiR improved image quality and visualization of distal coronary artery segments in 70 obese subjects with a mean BMI of 33 kg/m2 without increasing image noise and radiation dose.43 In a study of 78
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obese patients with a BMI >30 kg/m2, low-dose CTA (100 kVp) using SAFIRE reconstruction resulted in similar image quality and 50% lower radiation dose compared to standard tube potential CTA (120 kVp) with FBP reconstruction, suggesting that low-dose coronary CTA could also be performed in this population.44
5.2. Coronary CTA in patients with extensive coronary artery calcification Studies evaluating the effect of IR in relation to the limitations imposed by extensive coronary artery calcification on the assessment of luminal stenosis have shown mixed results. Among 55 consecutively evaluated patients with Agatston scores 400, calcium volume was lower and image quality improved using IRIS reconstruction compared to FBP. More importantly, there was an improvement in per-segment diagnostic accuracy measures using IR compared to FBP including specificity (95.8% vs 91.2%) and positive predictive value (76.9% vs 61.1%).45 Conversely, reduced diagnostic performance among patients with high coronary artery calcium score (CACS) compared to patients with low CACS was shown in another study of patients that underwent coronary CTA with iDose4 and ICA adjudication of stenosis severity, suggesting that the challenges encountered by blooming artifact are not completely removed by the use of IR.46
5.3.
Prior coronary stent implantation
It is well established that coronary stent evaluation is challenging in coronary CTA.47 IR studies have demonstrated both reduced volume of the stent struts in coronary CTA images reconstructed by IR compared to FBP23 and improved image quality and noise properties in the stented lumen with IR algorithms including 40% to 60% ASiR,48 IRIS,49 and iDose4.50 Most of these studies combined IR with a high-resolution kernel. In a study of 50 patients with 87 coronary stents undergoing ultra-low-dose coronary CTA before ICA, SAFIRE reconstructions were associated with improved subjective image quality and no difference in diagnostic accuracy measures compared to standard-dose FBP.51 The sensitivity, specificity, and positive and negative predictive values were 85%, 69%, and 32% and 96%, per stent using FBP and 100%, 75%, and 44% and 100% per stent using IR. Moreover, improved interobserver agreement for in-stent restenosis assessment was also shown in patients evaluated with iDose4 and a highresolution kernel compared to FBP with a standard cardiac kernel.52
6.
Effect on CACS
Multiple studies have evaluated the effect of IR on CACS. ASiR was associated with a reduced Agatston score, calcification volume, and mass.53 Of importance, in one study of 112 patients undergoing CACS assessment, the use of IR resulted in reclassification to a zero calcium score in 15 patients (13%) with an initial nonzero calcium score using FBP. In another study, increasing percentages of ASiR were
261
associated with a significant reduction in calcium sores and calcium volume but not mass compared to FBP.54 The results achieved with IRIS and SAFIRE have been variable. In one study, IRIS and SAFIRE had no significant effect on Agatston scores compared to FBP both in an in vitro model and in a retrospective cohort of 110 patients.55 Cardiac risk reclassification based on the Agatston score occurred in
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofCardiovascularCT.com
Review Article
Iterative reconstruction in cardiac CT Christopher Naoum MBBS, Philipp Blanke MD, Jonathon Leipsic MD* Department of Medical Imaging and Division of Cardiology, St Paul’s Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6
article info
abstract
Article history:
Iterative reconstruction (IR) has the ability to reduce image noise in CT without compro-
Received 17 March 2015
mising diagnostic quality, which permits a significant reduction in effective radiation dose.
Received in revised form
This been increasingly integrated into clinical CT practice over the past 7 years and has
15 April 2015
been particularly important in the field of cardiac CT with multiple vendors introducing
Accepted 15 April 2015
cardiac CTecompatible IR algorithms. The following review will summarize the principles
Available online 21 April 2015
of IR algorithms, studies validating their noise- and dose-reducing abilities, and the specific applications of IR in cardiac CT.
Keywords:
ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved.
Iterative reconstruction Cardiac computed tomography Coronary computed tomography Radiation dose
1.
Introduction
Since its introduction into clinical medicine over 40 years ago, CT has undergone tremendous technical advancements, some of the most important ranging from the development of slip ring technology to multiple-row detectors and electrocardiography (ECG) synchronization. Iterative reconstruction (IR), although currently perceived as a new technology, has in fact been available since the early 1980s with widespread use in nuclear medicine imaging. The lack of sufficient computational processing capabilities had precluded its routine use in clinical CT until recently. With its reintroduction in 2008, a number of new IR algorithms have been developed and undergone successful integration into clinical practice over the past 7 years. Given the widespread adoption and rapid development of this technology, an understanding of the pertinent
principles of IR and its clinical applications is of importance for clinicians involved in cardiac CT practice. Accordingly, the present review will provide an overview of the principles of IR, currently available clinical versions, and advancements in the application of IR in the field of cardiac CT.
2. General principles of reconstruction algorithms 2.1.
Filtered back projection
Until recently, CT images were almost exclusively reconstructed with filtered back projection (FBP), largely because of the fact that FBP generates diagnostic images at a low level of computational complexity. FBP operates on a simplified model
Conflict of interest: Jonathon Leipsic serves on the speaker’s bureau for GE Healthcare and is a consultant for HeartFlow. The other authors report no conflict of interest. * Corresponding author. E-mail address: [email protected] (J. Leipsic). 1934-5925/$ e see front matter ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved. http://dx.doi.org/10.1016/j.jcct.2015.04.004
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whereby the x-ray beam assumes a pencil shape and the x-ray source is aligned in a parallel fashion to a linear x-ray detector array. For image generation, the x-ray source is rotated over a predetermined angle, allowing for intensities to be measured at the detector. These intensities are described as an integral function for a specific angle and the shift in the position of the x-ray tube. After this, the reconstruction process involves solving an integral equation by inversion or so-called “back projection.” Despite its ability to rapidly reconstruct images, FBP has a number of limitations. In particular, they include increased image noise (which is most pronounced with low tube current imaging), poor contrast resolution, and streak artifacts. This is primarily due to the inherent failure of the FBP algorithm to account for image noise that results from Poisson statistical variations in the number of photons across the imaging plane and leads to the inverse relationship between radiation dose and image noise. Until the recent introduction of IR, therefore, lowering image noise could only be achieved at the expense of increased radiation dose. Attempts at “image-based denoising” through smoothing algorithms and IR filters (convolution kernels) allow for noise reduction but result in a compromise in image fidelity and spatial resolution.
2.2.
IR algorithms
IR techniques attempt to localize and selectively remove image noise through more “true” IR. This is achieved through a process of modeling of the imaging acquisition process including fluctuations in photon statistics, the optics system, and other aspects of x-ray interactions to generate an expected data set, which is then compared to the acquired data set. The differences between the 2 are used to identify and remove noise, and the process is repeated multiple times until the updated data converges with or approximates the expected data to maximally optimize the image. The first IR algorithm used in CT was the algebraic reconstruction technique, which reconstructed images through an iterative algorithm solving for linear algebraic equations and was the method of IR used in the very first CT scanner.1 Subsequent upgrades of this algorithm were developed but limited by their computational complexity,2 leading to the rapid adoption of the simpler technique of FBP. With recent advancements in computational power, however, IR re-emerged with statistical algorithms appearing first. Statistical IR deals with noise due to fluctuations in photon statistics by assigning a relatively higher weighting to data with low statistical uncertainty (low noise) and lesser weighting to data with high statistical uncertainty (high noise). It operates in either the “raw data domain” with subsequent reconstruction using the “noisereduced” data or in the “image domain” after IR. More recently, IR algorithms that model for the physical 3-dimensional nature of the system optics (geometric modeling of the focal point of the x-ray tube and pixel detector) and the interaction of photons in the transmission between the x-ray tube, isocenter, and detector (physical modeling) have also been developed and are collectively referred to as model-based IR (MBIR).3 Current IR algorithms typically combine statistical modeling with MBIR.
3. Radiation dose and noise reduction using IR algorithms in cardiac CT Growing concern in the last decade over patient radiation exposure was intensified by the Protection I study, which reported a median effective dose of 11.2 mSv across 47 sites for retrospectively gated cardiac CT and, more importantly, average doses of >25 mSv in some of the participating sites.4 Accordingly, a number of dose-reduction strategies have emerged. The simplest form of dose reduction, tube current reduction, has been limited in its implementation owing to its inverse relationship to image noise. With IR, however, diagnostic images can be achieved at lower tube currents, as the IR process reduces noise compared to FBP and therefore compensates some of the increased noise that would occur with FBP if tube current were lowered. Hence, effective dose can be significantly decreased while maintaining acceptable levels of image noise. Many studies have evaluated noise and dose reduction with IR algorithms across multiple vendors. These studies may be summarized as demonstrating either (1) improved noise properties with IR compared to FBP when images from the same patients are reconstructed using both algorithms (intraindividual analysis) or (2) preserved subjective image quality and quantitative noise properties among patients undergoing IR image reconstruction with low radiation dose techniques (reduced tube current and/or potential) compared to FBP algorithms with standard dose techniques (interindividual analysis). Specific IR algorithms used in cardiac CT and studies validating their noise- and dose-reducing abilities are discussed in the following sections.
3.1.
General Electric
3.1.1.
Adaptive Statistical Iterative Reconstruction
Adaptive statistical iterative reconstruction (ASiR; GE Healthcare, Milwaukee, WI), introduced in 2008, was the first IR algorithm used in cardiac CT.5 It operates in the raw data domain using FBP data as a building block and photon statistics to convert the measured pixel value to an idealized pixel value. ASiR is regarded a hybrid IR algorithm in that it can be blended with traditional FBP (at 10% thresholds). Early validation using ASiR was promising with the ERASIR trial documenting the possibility of a 44% dose reduction (4.1 mSv vs 2.3 mSv) while maintaining comparable image quality and noise properties compared to full-dose FBP coronary CT angiography (CTA) among prospectively enrolled patients at 3 sites.6 The best low-dose cardiac CTA results were obtained when a level of 40% to 60% ASiR was combined with FBP.7 Retrospective analyses showed comparable results, with one study demonstrating a 24% dose reduction among patients undergoing coronary CTA with ASiR reconstruction compared to FBP despite no differences in signal intensity, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), or diagnostic quality.8 Gosling et al9 demonstrated that while coronary CTA with FBP reconstruction resulted in a similar dose to invasive coronary angiography (ICA) (5.4 mSv vs 6.3 mSv), there was a 54% dose reduction using ASiR reconstruction (2.5 mSv) (Fig. 1).
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3.1.2.
VEO
VEO is a more complex algorithm that incorporates extensive modeling of system optics (MBIR) in addition to the statistical modeling performed in ASiR. Both experimental and clinical studies have been reported. One study of 3 ex vivo human donor hearts imaged by CT showed significantly improved image quality and CNR and reduced noise among MBIR reconstructions compared to FBP and ASiR.10 MBIR was also associated with improved plaque assessment using automated software, particularly in segments with moderate and severe calcification.11 More recently, in a single-center study of 42 patients, MBIR reconstruction permitted an 82% dose reduction using an ultra-low-dose coronary CTA scan protocol (80e100 kVp; 150e210 mAs, MBIR) compared to standard coronary CTA (100e120 kVp; 450e700 mAs, 30% ASiR) while preserving diagnostic image quality and enhancing SNR in the proximal coronary vessels.12
3.1.3.
Adaptive Statistical Iterative Reconstruction-V
GE Healthcare’s latest IR algorithm, ASiR-V, differs from previous generations by de-emphasizing system optics modeling and using more advanced noise and object modeling as well as introducing physics modeling. Through a reduced focus on optics modeling, ASiR-V reconstructions can be generated in significantly less time. Relative differences in subjective image quality are demonstrated in Fig. 2; however, studies validating the clinical utility of ASiR-V in coronary CTA are still needed.
3.2.
Philips
3.2.1.
iDose4
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Philips Healthcare (Best, the Netherlands) introduced “iDose4” in 2010, a unique IR algorithm that operates in both the raw and imaging data domains. Projection data is first analyzed to identify the noisiest measurements (poor SNR or low photon counts) by applying a model that includes photon statistics. Of importance, an iterative diffusion process is used that distinguishes noise from edges. This technique aims at preventing photon starvation artifacts (streaks, bias) before image creation. After this step, the noise is propagated to the image space but remains highly localized. Further structural modeling and dynamic model-based noise removal are applied iteratively in the image space to remove noise while preserving edges of true anatomic structures.13 Noise can be removed to varying levels depending on the need to image the heart at low dose vs improving image quality. iDose4 is particularly effective at generating images with reduced noise without creating the artificial appearance of images that has been typical of earlier generation IR techniques (Fig. 3).14 The effect of iDose4 in coronary CTA was studied in 200 consecutively referred patients sequentially assigned to FBP or IR. While achieving similar image quality, IR permitted a 39% dose reduction (2.8 1.4 mSv vs 4.6 3.0 mSv).15 Hou et al16 conducted a number of clinical studies validating iDose4. Among 109 patients undergoing ECG-gated helical 256-slice coronary CTA, IR performed with a 55% reduction in dose provided equivalent or improved coronary image quality
Fig. 1 e ASiR-V (GE Healthcare). Curved multiplanar reformats demonstrating the left anterior descending coronary artery with a coronary stent. Images are reconstructed with filtered back projection (A) and ASiR-V 50% (B) and 80% (C). ASiR, adaptive statistical iterative reconstruction. Images courtesy of Dr Ricardo Cury, Baptist Hospital, Miami.
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Fig. 2 e iDose4 and IMR (Phillips). Curved multiplanar images demonstrating a high-grade stenosis in the proximal left anterior descending coronary artery. Images are reconstructed using filtered back projection (A), iDose4 (B), and IMR (C). IMR, Iterative Model Reconstruction. Images courtesy of Philips Healthcare.
compared to FBP. The optimal level of iDose4 tube current reduction that could be achieved without compromising image quality was 63% in phantom and clinical studies using prospective ECG-gated 256-slice CTA.17,18 Improved image quality (CNR, visualization of distal vessels, and number of interpretable segments) and interobserver agreement were also shown in another study of 20 patients undergoing coronary CTA using iDose4 and FBP reconstruction.19
3.2.2.
Iterative Model Reconstruction
Iterative Model Reconstruction (IMR), a knowledge-based IR algorithm that significantly improves low-contrast resolution, was recently introduced. Clinical studies showed an additional improvement in subjective image quality and noise properties using IMR compared with both hybrid IR techniques and FBP among patients undergoing prospectively ECG-triggered coronary CTA performed at low tube voltage
(100 kVp) using a 256-slice scanner.20 IMR led to >80% intravascular noise reduction compared to FBP and improved image quality at 80% lower radiation exposure compared to standard techniques with FBP21 (Fig. 3).
3.3.
Siemens
3.3.1.
Iterative Reconstruction in Image Space
Iterative Reconstruction in Image space (IRIS) was released in 2008 by Siemens Healthcare (Forchheim, Germany).22 Unlike other IR algorithms, IRIS is based in the image domain. This means that an initial image is reconstructed from the acquired raw data. Subsequent repeated applications of the IR algorithm only use the image data (not the acquired raw data) to reduce image noise and enhance object contrast. In dose comparison studies, similar image quality was shown among 12 patients imaged with standard tube voltage
Fig. 3 e ADMIRE (Siemens). Curved multiplanar reformats demonstrating a proximal right coronary artery noncalcified plaque causing luminal stenosis reconstructed with filtered back projection (A) and ADMIRE (B). ADMIRE, Advanced Model Iterative Reconstruction. Images courtesy of Dr Stephan Achenbach and Dr Mohamed Marwan, Erlangen University, Erlangen.
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coronary CTA (120 kVp) and FBP and 12 matched patients imaged at lower tube voltage (80e100kVp) and IRIS reconstruction using a 62% dose reduction.23
3.3.2.
Sinogram Affirmed Iterative Reconstruction
Siemens subsequently introduced a raw data space IR algorithm in 2010, Sinogram Affirmed Iterative Reconstruction (SAFIRE), which operates in both the raw and image space domains. It uses FBP as a backbone and integrates a correction loop whereby a dynamic noise model is repeatedly applied to reduce image noise. A second correction occurs in the image space where noise is removed through statistical optimization based on knowledge of how the noise in the raw data is propagated to the image space.24 A number of strength levels are available (between 1 and 5) to allow for various degrees of blending IR reconstruction with FBP reconstruction, which influences the balance between noise reduction and image appearance.25 SAFIRE is a robust algorithm and is time efficient with 20 images reconstructed per second.26 Multiple studies have consistently validated the ability of SAFIRE to reduce image noise and therefore radiation dose. In a study of 60 patients that underwent standard coronary CTA with FBP followed by a second acquisition using 50% of initial tube current and reconstructed with SAFIRE, image quality and diagnostic accuracy using ICA as the reference standard was maintained despite a 52% reduction in radiation dose exposure.27 SAFIRE also led to improved image quality in coronary CTA acquisitions using tube currents reduced by as much as 80%.28 Reduced radiation dose was also achieved in a combined water phantom and clinical study of 49 patients using retrospective ECG gating with a dual-source CT (DSCT) scanner and SAFIRE reconstruction without compromising image quality.29 Finally, even the feasibility of very low-dose coronary CTA has also been demonstrated. In 50 patients that underwent prospectively ECG-triggered DSCT (0.66 0.05 mSv), subjective image quality and noise properties were significantly better with SAFIRE compared to FBP reconstructions.30
3.3.3.
Advanced Model Iterative Reconstruction
The latest Siemens IR algorithm, Advanced Model Iterative Reconstruction (ADMIRE), builds on SAFIRE but uses more advanced modeling to improve image resolution and edge detection in addition to noise reduction. Recently, reduced image noise and improved image quality compared to FBP were shown when low-dose coronary CTA (0.3 0.03 mSv) was performed using ADMIRE reconstructions31 (Fig. 3).
3.4.
Toshiba
3.4.1.
Adaptive Iterative Dose Reduction (AIDR/AIDR 3D)
The first algorithm introduced by Toshiba Medical Systems (Otawara, Japan), Adaptive Iterative Dose Reduction (AIDR) operated primarily in the image domain. The original highnoise images experience multiple iterative loops to achieve the appropriate noise levels.32,33 This technique has been replaced by a new technique using a 3-dimensional processing algorithm (AIDR-3D).34 This allows for a morphing of this reconstruction algorithm from the image domain to the raw data space. Both quantum and electrical noise from the x-ray photons and the CT system, respectively, are modeled.
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Moreover, statistical noise and scanner-specific geometric models are used to help reduce image noise (Fig. 4). Improved image quality with reduced radiation dose has been demonstrated with AIDR-3D compared to both AIDR and FBP in a total of 942 patients undergoing coronary CTA using 1 of the 3 reconstruction algorithms.35 Studies with 50% simulated dose reduction and AIDR-3D reconstruction have shown image quality that was at least comparable to standard coronary CTA imaging with FBP.36
4.
Effect on plaque assessment
IR changes image appearance compared to standard FBP reconstructions (to various degrees depending on the specific IR method that is applied). There is concern that this may affect the ability of CT to identify stenoses and characterize plaque in the coronary arteries. Multiple studies have therefore evaluated the effect of IR algorithms on the accuracy of plaque stenosis and composition assessment. Preserved diagnostic accuracy and subjective image quality were demonstrated in 60 patients who prospectively underwent 2 coronary CTA scans before ICA, which was used as the reference standard. The first scan was performed using standard radiation dose settings and FBP reconstruction and the second using 50% tube current-time reduction and SAFIRE reconstruction.27 Similar results were also observed at ultralow CTA dose (0.58 0.17 mSv) using SAFIRE combined with ECG-triggered high-pitch spiral acquisition.37 Comparable diagnostic accuracy was also shown between FBP reconstruction and SAFIRE reconstruction using only 50% of the projections by discarding data from one of the tube-detector systems (therefore simulating half radiation dose) in 65 consecutive patients who underwent DSCT.26 In one study of 50 patients undergoing coronary CTA, the best diagnostic performance (not statistically significant) was observed with strength factor 3, which was 95% accurate for diagnosing a >50% stenosis using ICA as the reference standard. Of interest, among 126 of 593 segments (in 36 of 50 patients) with significant stenosis (>50% on ICA), appropriate reclassification from false positive to true negative on coronary CTA occurred in 9 segments with severe calcification.38 Studies evaluating the effect of IR algorithms on plaque volume and composition assessment have generally demonstrated minimal effect on quantified volume but a tendency toward lower percentage of high-attenuation plaque compared to FBP. In one study of 9 ex vivo coronary arteries, CT generally overestimated plaque burden compared to intravascular ultrasonography (10 10%), whereas there was no difference between FBP, ASiR, or MBIR reconstructions.39 Similarly, ASiR did not result in a significant difference in plaque volume by automated plaque assessment software among 29 consecutive patients with 50 lesions but did result in a tendency to more soft and intermediate plaque components compared to FBP. When stratified by Hounsfield Units (HU), the percentage of plaque volume with attenuation values between 400 HU and 500 HU decreased significantly using ASiR.40 In a coronary CTA study of 63 patients with 55 coronary plaques, iDose4 (at 3 different levels) had no effect on plaque volume, composition, or luminal area assessment
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Fig. 4 e AIDR-3D (Toshiba). Axial cardiac CTA images demonstrating significantly less noise with AIDR-3D reconstruction (A) with noise value of 37.1 within the region of interest as compared to FBP with a noise value of 102.7. This was realized while maintaining image signal 829.8 vs 831.4. (B) despite similar signal intensity. Curved multiplanar reformats of the right coronary artery are demonstrated for AIDR-3D (C) and FBP (D) with the insets highlighting differences in coronary artery image quality between reconstruction algorithms. AIDR, Adaptive Iterative Dose Reduction; CTA, CT angiography; FBP, filtered back projection; HU, Hounsfield units. Images courtesy of Dr Marcus Chen, NIH, Bethesda.
compared to FBP.41 In a recent study of 3 ex vivo hearts, 173 cross-sectional coronary segments were coregistered between 3 different reconstruction methods (FBP, ASiR, MBIR) and histology. MBIR was more accurate for the detection of histologically verified lipid core plaque compared to both ASiR and FBP.42 In summary, there are still limited data regarding the ability of IR to improve coronary plaque detection and characterization, but there is justified hope for improved coronary plaque characterization in the future.
5. Applications of IR in specific patient populations Although dose reduction is the primary goal of IR in cardiac CT, there are some patients where noise properties are
unacceptable even if higher tube currents are used, for example, patients with elevated body mass index (BMI) and patients with extensive coronary artery calcification or prior coronary stenting. The ability to reduce noise with IR offers an opportunity to image patients that previously posed a significant problem for coronary CTA.
5.1.
Elevated BMI
Studies primarily evaluating the utility of IR in improving image quality of coronary CTA among patients with elevated BMI have demonstrated positive results. ASiR improved image quality and visualization of distal coronary artery segments in 70 obese subjects with a mean BMI of 33 kg/m2 without increasing image noise and radiation dose.43 In a study of 78
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obese patients with a BMI >30 kg/m2, low-dose CTA (100 kVp) using SAFIRE reconstruction resulted in similar image quality and 50% lower radiation dose compared to standard tube potential CTA (120 kVp) with FBP reconstruction, suggesting that low-dose coronary CTA could also be performed in this population.44
5.2. Coronary CTA in patients with extensive coronary artery calcification Studies evaluating the effect of IR in relation to the limitations imposed by extensive coronary artery calcification on the assessment of luminal stenosis have shown mixed results. Among 55 consecutively evaluated patients with Agatston scores 400, calcium volume was lower and image quality improved using IRIS reconstruction compared to FBP. More importantly, there was an improvement in per-segment diagnostic accuracy measures using IR compared to FBP including specificity (95.8% vs 91.2%) and positive predictive value (76.9% vs 61.1%).45 Conversely, reduced diagnostic performance among patients with high coronary artery calcium score (CACS) compared to patients with low CACS was shown in another study of patients that underwent coronary CTA with iDose4 and ICA adjudication of stenosis severity, suggesting that the challenges encountered by blooming artifact are not completely removed by the use of IR.46
5.3.
Prior coronary stent implantation
It is well established that coronary stent evaluation is challenging in coronary CTA.47 IR studies have demonstrated both reduced volume of the stent struts in coronary CTA images reconstructed by IR compared to FBP23 and improved image quality and noise properties in the stented lumen with IR algorithms including 40% to 60% ASiR,48 IRIS,49 and iDose4.50 Most of these studies combined IR with a high-resolution kernel. In a study of 50 patients with 87 coronary stents undergoing ultra-low-dose coronary CTA before ICA, SAFIRE reconstructions were associated with improved subjective image quality and no difference in diagnostic accuracy measures compared to standard-dose FBP.51 The sensitivity, specificity, and positive and negative predictive values were 85%, 69%, and 32% and 96%, per stent using FBP and 100%, 75%, and 44% and 100% per stent using IR. Moreover, improved interobserver agreement for in-stent restenosis assessment was also shown in patients evaluated with iDose4 and a highresolution kernel compared to FBP with a standard cardiac kernel.52
6.
Effect on CACS
Multiple studies have evaluated the effect of IR on CACS. ASiR was associated with a reduced Agatston score, calcification volume, and mass.53 Of importance, in one study of 112 patients undergoing CACS assessment, the use of IR resulted in reclassification to a zero calcium score in 15 patients (13%) with an initial nonzero calcium score using FBP. In another study, increasing percentages of ASiR were
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associated with a significant reduction in calcium sores and calcium volume but not mass compared to FBP.54 The results achieved with IRIS and SAFIRE have been variable. In one study, IRIS and SAFIRE had no significant effect on Agatston scores compared to FBP both in an in vitro model and in a retrospective cohort of 110 patients.55 Cardiac risk reclassification based on the Agatston score occurred in
