Purpose of Review The aim of this review is to highlight recent advancements, current trends, and the expanding role for cardiac CT (CCT) in the evaluation of ischemic heart disease, nonischemic cardiomyopathies, and some specific congenital myocardial disease states. Recent Findings CCT is a highly versatile imaging modality for the assessment of numerous cardiovascular disease states. Coronary CT angiography (CCTA) is now a well-established first-line imaging modality for the exclusion of significant coronary artery disease (CAD); however, CCTA has modest positive predictive value and specificity for diagnosing obstructive CAD in addition to limited capability to evaluate myocardial tissue characteristics. Summary CTP, when combined with CCTA, presents the potential for full functional and anatomic assessment with a single modality. CCT is a useful adjunct in select patients to both TTE and CMR in the evaluation of ventricular volumes and systolic function. Newer applications, such as dynamic CTP and DECT, are promising diagnostic tools offering the possibility of more quantitative assessment of ischemia. The superior spatial resolution and volumetric acquisition of CCT has an important role in the diagnosis of other nonischemic causes of cardiomyopathies. . . . . Keywords Cardiac CT CT perfusion Myocardial assessment Cardiomyopathy Dual-energy CT Introduction stemming this pattern. Increased focus on improved diagnos- tic techniques has fueled a rapid expansion in advanced car- Cardiovascular disease remains the worldwide leading cause diovascular imaging techniques over the last two decades. of morbidity and mortality accounting for up to 31% of all Cardiac CT (CCT), specifically coronary CT angiography deaths . This trend continues to drive efforts to develop (CCTA), has been well established for the evaluation of symp- advanced detection and therapeutic modalities in hopes of tomatic patients with stable or acute chest pain and concern for coronary artery disease (CAD) [2, 3]. Numerous studies have demonstrated a very high negative predictive value (~ 99%) for the exclusion of CAD. Conversely, the positive predictive This article is part of the Topical Collection on Cardiac Computed value of CCTA is modest (60–80% depending on the study) in Tomography patients with a high pretest probability of obstructive CAD or those with unfavorable conditions for high-quality imaging * Dustin M. Thomas email@example.com such as rapid heart rates and significant plaque calcifications . The diagnostic power of gadolinium-enhanced cardiac Cardiology Division, Department of Medicine, San Antonio Military magnetic resonance (CMR) in the evaluation of ischemic heart Medical Center, San Antonio, TX, USA disease and cardiomyopathies has been well established and is Cardiology Division, Department of Medicine, Tripler Army the preferred diagnostic test when the distinction between Medical Center, Honolulu, HI, USA these conditions is needed in a single study. Recent studies Division of Cardiology, Department of Radiology, The George have demonstrated similar shared characteristics in myocardi- Washington University School of Medicine, Washington, DC, USA al distribution and flux between iodinated contrast and gado- Cardiology Division, University of Washington, Seattle, WA, USA linium, particularly when iodinated contrast is coupled with 16 Page 2 of 16 Curr Cardiovasc Imaging Rep (2018) 11:16 X-ray photon attenuation profiles within the myocardium [5� ]. Myocardial Imaging in Ischemic Heart Disease These findings have led to expanded applications of CCT in the evaluation of ischemic heart disease and cardiomyopathies Anatomy Versus Physiology in the Evaluation of CAD (references in comments) [6, 7, 8�� ]. Myocardial assessment in ischemic heart disease encompasses both the anatomical assessment of the cardiac dimensions and structure as well as indirectly assessing coronary artery steno- CCT for Chamber Size and Function sis severity and CAD chronicity. There is a complex interac- Assessment tion between observed coronary anatomy (i.e., luminal steno- sis) and the presence of ischemia. Published data demonstrates Transthoracic echocardiography (TTE) is the most widely that a luminal stenosis ≥ 50% by CCTA correlates poorly with available and commonly used technique for assessing cardiac myocardial ischemia by either single-photon emission com- structure and function. However, TTE assessment may be puted tomography (SPECT) or positron emission tomography suboptimal in certain subsets of patients, namely those with (PET) with positive predictive value (PPV) ranging from 29 to poor imaging windows due to lung disease, obesity, chest wall 58% . Conversely, ischemia is still present in up to 12% of defects, or overlying dressings in burn and post-surgical pa- patients with ≥ 50% stenosis . The same is true for inva- tients. CMR imaging is a powerful adjunctive test in these sive coronary angiography (ICA). Furthermore, revasculariza- patients and is the current gold standard for assessment of tion based on ICA stenosis alone does not reduce death or cardiac volumes and systolic function. Compared with TTE nonfatal MI compared with medical therapy . and CMR, CCT has superior spatial resolution with decreased Physiologic assessment with invasive fractional flow reserve but comparable temporal resolution [9, 10]. Quantification of (iFFR) demonstrated that an intervention guided by vessel- ventricular volumes and function requires acquisition of a full specific ischemia for patients with indeterminate stenosis re- cardiac cycle, or R-R interval, which requires retrospective, sulted in 33% less percutaneous coronary interventions and ECG-gated scanning in most scanner platforms. While early 30% improvement in composite cardiovascular outcomes [18, studies reported effective radiation doses of at least 10– 19]. Given these robust data, many suggest that iFFR is the 14 mSv utilizing retrospective acquisition and 64-slice multi- gold standard for ischemia assessment. The ongoing detector CT (MDCT) scanner platforms, the latest genera- ISCHEMIA trial (NCT01471522) will inform the discussion tion scanner platforms have achieved doses as low as regarding outcomes with revascularization based solely on 3.8 mSv in select patients [11–13]. In head-to-head com- ischemia. In the meantime, CCT with CCTA is positioned as parison studies, CCT-derived ventricular volumes and the single modality capable of simultaneously evaluating cor- ejection fraction (EF) have excellent correlation with onary artery anatomy and CAD burden and assessment of CMR and may be superior to both 2D and 3D echo [14� ]. physiologic myocardial blood flow. When viewed in cine mode on a 3D workstation, CCT can be used for the evaluation of regional wall motion changes in both the left ventricle (LV) and right ventricle (RV). To Multimodality Myocardial Imaging optimize acquisition and limit contrast exposure, contrast in Ischemic Heart Disease bolus injection should be tailored to the ventricle of inter- est. In LV-only imaging, scan triggering and injection pro- The last decade has witnessed a shift in the diagnostic ap- tocols similar to those utilized for CCTA can be utilized. If proach for ischemic heart disease away from the utilization biventricular assessment is needed, special attention of a single functional testing modality followed by ICA to a should be paid to the contrast injection protocol to allow patient-centered multimodality approach. This approach takes for uniform contrast opacification of the chamber of inter- into account patient parameters, preferences, and radiation est while minimizing mixing and beam-hardening artifacts dose considerations to guide therapy. As such, providers common in the right heart. This typically requires a tasked with the evaluation of ischemic heart disease need a triphasic injection protocol utilizing a standard initial con- baseline understanding of the strengths and limitations of trast injection (4–6 mL/s) followed by a saline/contrast available modalities to allow for a multimodality imaging ap- mixture (possibly at a lower injection rate of 2–3mL/s) proach to these patients. to maximize right-heart opacification and minimizing blood/contrast swirling, and completed with a saline bolus. Single-Photon Emission Computed Tomography CCT-derived RV measurements show excellent correlation with CMR and can be especially useful in congenital heart SPECT is a static imaging modality that leverages differential disease patients (such as tetralogy of Fallot) and in whom distribution and uptake of modest energy (70–120 keV) radio- implantable cardiac devices are already present . tracers within the myocardium based on differences in Curr Cardiovasc Imaging Rep (2018) 11:16 Page 3 of 16 16 coronary blood flow and myocardial viability. SPECT imag- addition of intravenous gadolinium allows for both first- ing, compared to iFFR, has a sensitivity of 74% and specific- pass stress imaging, utilizing gradient echo sequences, ity of 79% for the diagnosis of significant obstructive CAD for the assessment of myocardial ischemia [32, 33]. . Important limitations of SPECT imaging include diffi- Compared to SPECT and ICA, stress CMR assessment culty in diagnosing high-risk CAD in the setting of balanced of ischemia was found to have a sensitivity of 89% for ischemia (i.e., global low, but homogenous blood flow), poor both and specificity of 76 and 87%, respectively [21, spatial resolution and image quality in obese patients, and 34–37]. Performance of late gadolinium enhancement effective radiation doses that average 12–15 mSv for stress- (LGE) sequences provides information on the presence rest protocols [21, 22]. Obesity-related artifacts can be miti- and location of myocardial infarction, as well as robust gated with attenuation correction or prone imaging, though prognostic information. Additionally, the transmural ex- these techniques can lead to artefactual perfusion defects that tent of LGE uptake serves as a powerful tool in the require the reader to synthesize data from multiple acquisi- evaluation of viability. Beyond the evaluation of ische- tions and can increase imaging time [23, 24]. Additionally, mic heart disease, mid-myocardial and/or epicardial up- several academic centers have implemented protocols to re- take of LGE can also signal the presence of other infil- duce radiation dose to include routine use of half-dose acqui- trative and inflammatory cardiomyopathies, such as sar- sitions resulting in 5–6 mSv doses . The advantages of coidosis or idiopathic myocarditis. CMR with or without SPECT imaging are the ability to perform testing in patients stress has its limitations. Notably, it is an expensive, that can or cannot exercise, in virtually all heart rhythms, and time-consuming exam (often requiring 30–60 min), is in known CAD and prior coronary revascularization. poorly tolerated in patients with severe claustrophobia, Additionally, there is data demonstrating the ability of and requires multiple (sometimes prolonged) breath SPECT to assess viability, albeit with significantly reduced holds, and gadolinium should not be used in patients sensitivity when compared to PET or CMR [26� , 27]. with renal dysfunction (GFR < 30). Additionally, the Finally, dynamic SPECT techniques currently being validated presence of ferrometallic materials within the myocardi- offer the promise of quantifying myocardial blood flow utiliz- um can create signal voids and limit the diagnostic utility ing SPECT tracers . of CMR even in those with MR conditional devices. Positron Emission Tomography CCT in the Assessment of Ischemic Heart PET is a versatile nuclear imaging modality that detects Disease high-energy (512 keV) photons that result from an anni- hilation interaction between a positron and a valence elec- CCT is an emerging application with the potential to deliver tron. In addition to static perfusion data, the radiotracers coronary anatomy and functional significance in a single scan. Rb-82 and 13N-ammonia can be used to quantify absolute Utilizing vasodilator stress agents, CCT is able to assess dif- coronary blood flow and coronary flow reserve [29, 30]. ferences in myocardial distribution of iodinated contrast, a Viability assessment can also be performed utilizing the technique referred to broadly as cardiac CT perfusion (CTP) glucose analog fluorodeoxyglucose (FDG) by leveraging [38� ]. CTP protocols can differ based on the scanner platform the difference in metabolic properties between infarcted being used, the information that is needed, and the desired and hibernating tissues. When combined with anatomic patient throughput. Based on the protocol selected, the possi- CCT imaging (CAC and/or CCTA), the diagnostic perfor- bility exists to obtain detailed coronary anatomy (with mance of PET imaging for the diagnosis of CAD is great- CCTA), either first-pass (dynamic) or static stress perfusion ly increased with a reported sensitivity of 90% and spec- information, stress and/or resting wall motion and EF, and CT ificity of 95% . The radiation cost of PET is modest at delayed enhancement (CTDE) for the detection of myocardial 2–4 mSv with the primary limitation to more widespread infarction. Additionally, newer CT applications, such as dual- use of this technology limited primarily by the cost, lim- energy CT (DECT), show significant promise in the ability to ited scanner locations, limited available readers, and un- further discriminate myocardial contrast uptake by leveraging availability or expense of stress radiotracers. the differences in attenuation profiles between tissues and contrast agents at different tube voltages. The accuracy of Cardiac Magnetic Resonance static CTP imaging (Table 1) compared to SPECT for predicting obstructive CAD on ICA is up to 96% sensitivity CMR is the gold standard for the assessment of cardiac and 98% specificity, on a per vessel basis, with a PPV up to structure and function. Additionally, with emerging ap- 94% and a negative predictive value (NPV) up to 98% [39, 40, plications such as T1 mapping, CMR is the best validat- 42, 43, 45–48, 63, 64]. CTP has a sensitivity and specificity of ed noninvasive modality for tissue characterization. The 82 and 87% compared to stress CMR, respectively, for the 16 Page 4 of 16 Curr Cardiovasc Imaging Rep (2018) 11:16 Table 1 Review of current CTP literature Author (year) No. of CT scanner Comparator Sensitivity Specificity PPV % NPV % patients % % Static Blankstein et al. (2009)  34 64-slice DSCT SPECT 84 80 71 90 Rocha-Filho et al. (2010) 35 64-slice DSCT QCA 91 91 86 93  Feuchtner et al. (2011)  30 128-slice DSCT Stress CMR 96 88 93 94 Cury et al. (2011)  26 64-detector SPECT 94 78 89 87 Ko et al. (2012)  42 320-detector SPECT 76 84 82 79 Ko et al. (2012)  40 320-detector iFFR 74 66 56 81 George et al. (2012)  50 320-detector SPECT 50 89 55 87 Nasis (2013)  20 320-detector QCA w/ SPECT 94 98 94 98 Rochitte et al. (2014)  381 320-detector SPECT and ICA 80 74 65 86 Osawa et al. (2014)  145 128-slice DSCT ICA 85 94 79 96 Cury et al. (2015) [38� ] 110 Multivendor SPECT 90 84 36.67 99.97 reversible.fixed reversible.fixed Dynamic Kido et al. (2008)  14 16-detector SPECT 87 79 50 96 Bastarrika et al. (2010)  10 128-slice DSCT Stress CMR 86 98 94 96 Ho et al. (2010)  35 128-slice DSCT SPECT 83 78 79 82 Bamberg et al. (2011)  33 128-slice DSCT iFFR 93 87 75 97 So et al. (2012)  26 64-detector MPR vs. SPECT 95 35 83 67 Wang et al. (2012)  30 128-slice DSCT SPECT and ICA 85/90 92/81 55/58 96/96 Weininger et al. (2012)  20 128-slice DSCT Stress CMR 86 98 94 96 Rossi et al. (2013)  80 128-slice DSCT iFFR 88 90 77 95 Greif et al. (2013)  65 128-slice DSCT iFFR 95 74 48 98 Huber et al. (2013)  32 256-detector iFFR 76 100 10 91 Bamberg et al. (2014)  31 128-slice DSCT Stress CMR 78/100 75/75 51/92 91/100 Magalhaes et al. (2015)  381 320-detector SPECT and ICA 98/58 96/86 96/55 98/87 Baxa et al. (2015)  54 128-slice DSCT ICA 97 95 95 98 Wichman et al. (2016)  71 128-slice DSCT Visual assessment 100 88 43 100 Summary of data supporting CTP utilizing both static and dynamic protocols ICA invasive coronary angiography, iFFR invasive fractional flow reserve, CMR cardiac magnetic resonance imaging, SPECT single-photon emission computed tomography, QCA quantitative coronary assessment/analysis, MPR myocardial perfusion reserve, DSCT dual-source CT detection of myocardial ischemia . The addition of CTDE dynamic CTP acquisitions. Static CTP imaging refers to im- allows for the assessment of myocardial viability with report- aging that takes place at or near peak contrast opacification of ed sensitivities of 72–77% and specificities of 88–92% when the left heart and involves acquisition of a single dataset. compared to LGE by CMR . The following sections ex- Dynamic CTP imaging takes sequential datasets during the pand upon CTP protocol selection, post-processing consider- initial pass of iodinated contrast from the venous to arterial ations, and CTP techniques. circulation. On both static and dynamic CTP imaging, regions of hypoperfusion will appear as low attenuation regions with- in a vascular distribution, typically worse in the subendocar- dial layer than the epicardial layer. In addition, software pack- CT Perfusion Protocols ages available within the 3D workstation may allow for gen- eration of attenuation-based color mapping and attenuation CTP relies on the kinetic properties of iodinated contrast as it is distributed and taken up into myocardial tissue. CTP imag- indexing, as well as a semiquantitative assessment using a transmural perfusion ratio (TPR). TPR is simply the ratio of ing involves rest and stress acquisitions and can be performed in a static or dynamic method. Figure 1 depicts the most com- the average Hounsfield unit (HU) attenuation of a region of interest (ROI) within the subendocardial layer compared with monly used CTP protocols, which apply both to static and Curr Cardiovasc Imaging Rep (2018) 11:16 Page 5 of 16 16 Fig. 1 Graphical representation of two of the most common CTP ECG-gated acquisition (may vary based on scanner platform). protocols used. a Rest-stress protocol—standard patient preparation for Adenosine is preferred given its short half-life, preventing carryover CCTA is recommended prior to the acquisition of rest images. Vasodilator hyperemia and hemodynamic changes into the rest acquisition. After a infusion can be started within the last 3–5 min of the washout phase to 5–15-min delay, DE images can be obtained (IV nodal blocking agents facilitate throughput. Finally, a 5–15-min delay is standard prior to can be given prior to acquisition if needed). Finally, additional nodal prospective ECG-triggered acquisition for DE assessment. Total time blockers are administered followed by nitroglycerin prior to ECG- protocol time is approximately 20–40 min. b Stress-rest protocol— triggered prospective rest series acquisition vasodilator stress agent is given upfront followed by retrospective the average HU attenuation within the same ROI of the epi- on wide-detector scanner platforms, a full R-R interval cardial layer (Fig. 2). This approach highlights the well- acquisition. This allows for assessment of any stress- described phenomena of an ischemic gradient worse in the induced wall motion changes. Finally, a delayed, subendocardial myocardial layers and gradually improving noncontrast-enhanced dataset can be added approximately moving closer to the epicardial coronaries. The use of TPR 10 min after the stress acquisition to evaluate for evidence in static CTP significantly improves diagnostic accuracy when of infarction. The advantage to this approach is the deferral compared to other techniques [45, 67]. of the stress acquisition when rest images either show nonobstructive CAD (no stenosis ≥ 50%) or a high-grade stenosis (≥ 70%). If stress imaging is pursued, a delay of Rest-Stress Static CTP 10–20 min following rest imaging should be implemented to ensure adequate contrast washout. ECG-based tube cur- Rest first, followed by stress image acquisition protocol, is the most widely used in clinical practice and is best suited rent modulation is recommended to reduce radiation dose for low- to intermediate-risk patients without known CAD . In addition to the evaluation of stable chest pain in the (Fig. 1a). This protocol involves an initial rest acquisition outpatient setting, rest-stress CTP protocols may be ideal similar to simple CCTA in which an initial CAC followed for the evaluation of acute chest pain in the emergency by a prospective, ECG-triggered, contrast-enhanced CCTA department, leveraging both the quality data and high is obtained first. Inherent in this is the fact that patients are NPVof CCTA in the ED with the ability to further evaluate prepped in a standard fashion with nodal blocking agents indeterminate lesions and incrementally increase appropri- and sublingual nitroglycerin. If an indeterminate stenosis is ate disposition . The main limitations to rest-stress CTP protocols are the need to pretreatment with nitroglyc- detected, a vasodilator stress dataset is subsequently ob- tained. Depending on the scanner platform being used, this erin and nodal blocking agents prior to rest acquisitions, which can mask ischemia, similar to data seen in SPECT will either entail a retrospective, ECG-gated acquisition or, 16 Page 6 of 16 Curr Cardiovasc Imaging Rep (2018) 11:16 Fig. 2 The left-sided images depict a thick-slab three-chamber average suggestive of ischemia. The right-sided image represents available attenuation reconstruction (WW/WL 300/150) with a segment of the postprocessing application software available through various vendors apical septal wall segment magnified to better demonstrate where that allow for semiautomated calculation of TPR throughout the entire epicardial (epi) and subendocardial (endo) regions of interest (ROI) myocardium. Color overlay can be added to assist with visual assessment would be drawn. TPR is calculated by obtaining the average Hounsfield of ischemia. In the presented image, there is evidence of ischemia in the unit (HU) attenuation from a ROI within the endo (HUendo) and dividing LAD distribution. Of note, the apparent perfusion defect in the by the average HU derived from a ROI within the epi (HUepi) within the inferolateral wall segment represents a common artifact observed in same wall segment. A ratio < 1.0 is abnormal and ratios ≤ 0.75 are highly CTP and not true ischemia in the left circumflex distribution imaging . Additionally, residual circulating contrast only CTP and high-resolution coronary anatomy in a single, from rest imaging can contaminate the stress acquisition stress acquisition, mitigating the need for rest acquisition and and hinder the diagnostic performance. thus conserving radiation dose. Stress-Rest Static CTP Dynamic (First-Pass) CTP Less commonly used when compared to rest-stress, stress-first Static imaging techniques, with or without stress acquisitions, CTP is best suited for patients with intermediate to high pre- are limited to single snapshots in time and do not provide test risk known intermediate/indeterminate stenosis, or prior comprehensive blood flow analysis. Historically, limitations revascularization where the assessment of ischemia in a par- in scanner technology made static CTP the only viable meth- ticular vascular territory is favored over coronary anatomy od. However, the latest generation 256- and 320-row detector (Fig. 1b). When performing stress-first CTP, the pharmacoki- platforms allow for imaging of the entire cardiac volume with netics of the vasodilatory agents being used must be taken into a stationary table and a single gantry rotation. Additionally, account. Dipyridamole, adenosine, or regadenoson can all be second-generation dual-source CT (DSCT) can cover this used and achieve hyperemia at various time periods following same volume utilizing a table shuttle method. The third- administration and sustain hyperemia for variable durations. generation DSCT has increased z-axis coverage up to Adenosine, owing to its rapid metabolism and thus rapid off- 105 mm and, thus, can image the cardiac volume without set with cessation of infusion, was used in a majority of the the need for table shuttling [50, 51, 55, 71]. This technology validation studies. Regadenoson is also a viable option and is allows for the performance of first-pass perfusion owing to the the preferred agent in SPECT and CMR due to ease of admin- ability of these newer generation scanners to acquire full car- istration and a low side effect profile. The limitation of diac datasets in short succession, termed dynamic CTP. regadenoson stress-first CTP is to the persistence of heart rate Dynamic CTP allows for comparison of time-attenuation pro- elevation (30–40 min following regadenoson administration), files within myocardial segments, which facilitates direct making motion-free imaging of the coronaries challenging. quantification of myocardial blood flow (MBF) . MBF Newer CT scanners can overcome the heart rate elevation calculation by dynamic CTP involves mathematic modeling associated with regadenoson with the use of motion correction derived from the deconvolution methods used in CMR [52, software and faster gantry rotation speeds allowing for stress- 73]. In semiquantitative analysis, the time-attenuation curve Curr Cardiovasc Imaging Rep (2018) 11:16 Page 7 of 16 16 for a myocardial ROI is derived and a time-to-peak attenua- exposing the same sample volume to both a low (typically tion, attenuation upslope, and area under the curve are calcu- 80 kV) and high (140 kV) tube voltage. Utilizing monochro- lated. This is the most commonly used semiquantitative meth- matic reconstructions at these differing energy levels, subtle od as only the upslope time to peak attenuation is sampled, differences in tissue contrast uptake can be more readily de- thus lowering effective radiation dose. Dynamic CTP valida- tected. Specific to CTP, DECT facilitates creating of an iodine tion studies, utilizing 320-row MDCT and second-generation map that serves as a surrogate for blood flow . This is DSCT, have shown varying, but mostly positive results in accomplished by utilizing one of four vendor-specific technol- detection of hemodynamically significant CAD when com- ogies (Fig. 3): two X-ray sources offset by 90° operating at pared against ICA, CMR, and SPECT. Dynamic CTP (Table different energy levels, rapid switching utilizing a single 1) has demonstrated sensitivities ranging from 58 to 100%, source where the X-ray tube cycles rapidly between low and specificities from 74 to 100%, NPV 82–100%, and PPV 43– high tube voltage during a single gantry rotation, a dual layer 100% [51, 56, 57, 60]. The biggest limitation of dynamic CTP detector model where a single X-ray source provides a spec- is the relatively high radiation dose required (8.2 to 18.8 mSv trum of energy levels in the presence of a double-layered in validation studies) [62, 73]. Dynamic CTP represents an detector configuration that registers only high- and low- emerging CCT application and further research is needed be- energy photons, and gantry rotation kilovolt switching where fore more widespread implementation is pursued. a single X-ray source scans a full gantry rotation at high- and a full gantry rotation at low-energy settings of the same tissue Dual-Energy Computed Tomography volume (thus each volume is scanned twice) . With these specialized acquisitions, a virtual monochromatic image DECT was first introduced in 2008 and has undergone several (VMI) is generated that is less susceptible to beam hardening advancements and innovations in the last decade that have and other artifacts while maximizing the superior contrast seen with iodinated agents and soft tissue at low kilovolt set- significantly increased its diagnostic utility [74, 75]. DECT is based on the principles of the photoelectric effect and the tings [78–80]. DECT can readily delineate the iodinated con- energy-related attenuation difference of tissues observed with trast in the blood pool within the ventricle and within the Fig. 3 Representation of currently available vendor-specific dual-energy CT (DECT) solutions available to date 16 Page 8 of 16 Curr Cardiovasc Imaging Rep (2018) 11:16 vessels and absorbed by the myocardium and can then be used to make color-coded maps, similar to SPECT images, that detail myocardial perfusion [76, 81]. Compared with SPECT and single-energy CTP, DECT protocols (Table 2) are ob- served to have a sensitivity of 82–94%, specificity of 71– 94%, PPV of 53–91%, and NPV of 81–97% [84, 85]. Historically, one of the main limitations to DECTwas the high required radiation dose and high contrast volume . However, subsequent advancements have shown that the use of ultralow-energy levels (40–50 kV) enhances iodine contrast differences and improves the accuracy of delayed enhance- ment imaging, particularly forthe detectionofscar. Several studies of DECT have achieved radiation doses of Fig. 4 Thick-slab average HU short-axis projection demonstrating a 0.5 to 4.4 mSv, significantly reduced when compared to early perfusion defect in the LAD territory (black arrows). In the visual assessment of ischemia with CTP imaging, windowing at the 3D DECTor SPECT [88, 89]. Additionally, no reduction in image workstation is vital to maximize visual discrimination between ischemic quality was observed despite reductions in contrast volume myocardium (HU attenuation between 30 and 70) and normal approaching 50% [90, 91]. Currently, DECT for myocardial myocardium (HU attenuation ~ 100). As is commonly observed, a hypoattenuation artifact is present in the inferolateral wall segment perfusion is not routinely utilized in clinical practice as further secondary to beam hardening from the descending thoracic aorta (*) study is ongoing to determine the optimal energy settings and mimicking a perfusion defect in this territory to further investigate the various vendor-specific DECT solu- tions more thoroughly for cardiac imaging [92–94]. that measures the ratio of the average HU of the subendocar- dial to subepicardial tissue where a normal TPR has been defined as above 1 and a ratio of 0.75 or less suggests ischemia CTP Post-processing at the 3D Workstation . The combination of DE-CCT with TPR compared to SPECT demonstrates a sensitivity of 86%, specificity of Post-processing of CTP datasets relies on the visual assess- 92%, positive predictive value of 92%, and negative predic- ment of the ischemic myocardial segments in comparison to tive value of 85% for diagnosing clinically significant perfu- normally perfused myocardium (Fig. 4). Multiplaner sion defects. reformatted images allow for evaluation in the classic 17 seg- ment model view. Image display settings should be adjusted to thick MPR slabs (3–8mm) andminimum intensity projection Limitations of CTP (MinIP) or average HU attenuation projection as opposed to maximum intensity projection (MIP). This allows for more Radiation dose, as mentioned above, continues to be a limita- ready identification of ischemic segments. Finally, appropriate tion to widespread implementation of CTP protocols. Newer window width and level settings (200–300 and 100–150, re- generation scanners and the possibility of single acquisition spectively) should be utilized [39, 95]. These settings optimize CCTA and stress CTP hold promise for lowering radiation the displayed grayscale centering around the normal HU at- dose to levels more comparable to SPECT. Imaging artifacts, tenuation of the myocardium (average HU of 90–100) and the specifically beam hardening from the descending thoracic aor- narrow width accentuates ischemic or infarcted myocardium ta, can affect interpretation of the inferolateral wall segments ranging from subzero HU to 30 HU [96, 97]. TPR (Fig. 2), as by mimicking a perfusion defect in that territory. Utilization of discussed above, is a semiquantitative assessment of perfusion beta-blockers and nitrates, as is often required for acquisition Table 2 Review of current literature supporting dual-energy CTP Author (year) No. of patients CT scanner Comparator Sensitivity % Specificity % PPV % NPV % Ruzsics et al. (2009)  36 64-slice DSCT SPECT 92 93 83 97 Wang et al. (2011)  31 64-slice DSCT Stress CMR 89 78 74 91 Ko et al. (2011)  50 64-slice DSCT Stress CMR 89 78 74 91 Ko et al. (2012)  45 64-slice DSCT ICA 89 74 80 85 Kim et al. (2014)  50 128-slice DSCT Stress CMR 94 71 60 96 Summary of data supporting CTP utilizing both static and dynamic protocols ICA invasive coronary angiography, CMR cardiac magnetic resonance imaging, DSCT dual-source CT Curr Cardiovasc Imaging Rep (2018) 11:16 Page 9 of 16 16 of CCTA data, reduces the sensitivity of CTP scans by specificity of 97% . While a prospective, ECG- masking smaller, typically single-vessel, perfusion defects as triggered protocol is routinely used to minimize patient shown in the SPECT literature [98, 99]. Finally, as summa- radiation dose, full cardiac cycle imaging allows for the rized in Fig. 1a, a 10–20-min washout period is paramount assessment of wall motion and facilitates ventricular volu- when utilizing rest-stress acquisition protocols. Iodinated con- metric and EF assessment that correlate strongly with trast is slow to wash into (and subsequently out of) ischemic CMR [15, 106]. Several techniques including ECG-based territories. The presence of residual contrast in the myocardi- tube current modulation, low and ultralow kilovolt imag- um at the time of the second contrast bolus injection narrows ing, and iterative reconstruction have been used to reduce the attenuation profile differences between normal and ische- radiation dose in retrospective acquisition of images . mic myocardium, thus reducing the sensitivity for detection of When compared to TTE, SPECT, and CMR-based assess- ischemic defects. ments, the CT-derived measurements correlate well with an observed slight overestimation of LVEF. Specific to car- diomyopathies involving the RV, scan protocol changes Infarct Assessment Utilizing CTDE to the contrast bolus injection may be necessary in order to optimize RV opacification while minimizing blood- Over the last two decades, advancement in CMR with LGE contrast mixing and beam-hardening artifacts. A triphasic has revolutionized the assessment of myocardial fibrosis sec- contrast injection protocol involving an initial 100% con- ondary to infarction, infiltration, or inflammation. The ability trastbolus at aratebetween4and6mL/sfollowedbya of CMR to assess these various tissue states is based on the saline/contrast mix at a lower rate (~ 2 mL/s) and terminat- pathologic effects on the tissues resulting in changes in tissue ingwithasaline bolushas been showntoprovide optimal density and differential uptake of gadolinium. Iodinated con- right-sided chamber opacification . Table 3 highlights trast has similar kinetics and distribution to gadolinium CCT findings that can help to make a diagnosis. As allowing for the potential of DECT to detect infarction similar outlined above, appropriate protocol selection is vital in to CMR . As mentioned above, CTDE involves the ac- cardiomyopathies where regional wall motion, ventricular quisition of a delayed, noncontrast-enhanced dataset obtained volumes, or valve motion (SAM) is needed. As an exam- approximately 10 min after the last contrast-enhanced dataset. ple, Fig. 5 highlights the strengths of CCT in a patient with Similar to gadolinium imaging characteristics with CMR, in- apical-variant hypertrophic cardiomyopathy. CCT allows farcted tissues will have a delayed washout for iodinated con- for precise assessment of wall thickness and possible DE trast material and appear hyperenhancing [5� , 101]. Small if appropriately protocoled. Additionally, the apical studies have confirmed a correlation of 81–85% in the detec- aneurysm/pouch commonly encountered in apical-variant tion of infarction compared to CMR [102, 103]. The prognos- HCM is easily visualized, and though not present here, tic importance of DE findings on CT was assessed in a small thrombus formation would be easily diagnosed. study of 102 patients who showed a 19% rate of MACE at 2 years. Based on these results, CTDE was identified as an independent predictor of major adverse cardiovascular events (MACE) . Utilization of ultralow kiloelectron volt set- Myocardial Assessment with Hybrid Cardiac tings can reduce artifact and accentuate smaller areas of resid- Imaging (PET/CT) ual contrast uptake within the myocardium, though more stud- ies are needed . PET whencombinedwithCThas emerged asa powerful diagnostic modality, both in ischemic heart disease as well as various inflammatory and infiltrative disease pro- CCT in the Assessment of Nonischemic cesses. PET imaging is commonly undertaken to assess and Inheritable Cardiomyopathies the metabolic activity of tissue utilizing the glucose an- alog F-fluorodeoxyglucose (FDG). FDG PET imaging, CCT can serve as an important adjunctive modality to TTE taking advantage of differences in glucose metabolism in patients with known or suspected cardiomyopathies, pri- between normal myocytes and diseased myocytes, has marily in patients with claustrophobia, implantable cardiac the ability to detect hibernating myocardium in viability devices, and poor TTE windows. In the setting of newly testing and myocyte inflammation as seen in acute car- diagnosed heart failure with a reduced ejection fraction, diac sarcoidosis . Imaging these very different dis- CCTA is well validated to exclude significant CAD in pa- ease states requires significant preimaging patient prepa- tients with low to intermediate pretest risk of CAD. In ration involving standardized protocols meant to manip- patients with reduced EF less than 35%, CCTA for the ulate the glucose substrate environment available to evaluation of CAD has a reported sensitivity of 98% and myocytes . 16 Page 10 of 16 Curr Cardiovasc Imaging Rep (2018) 11:16 Table 3 Common findings by Cardiomyopathy CCT findings CCT in cardiomyopathies Dilated nonischemic cardiomyopathy � Global systolic dysfunction (NICM) � Dilated ventricle � Apical tenting of MV leaflets � Hypertrabeculation not meeting LVNC criteria � Absence of significant CAD Hypertrophic cardiomyopathy (HCM) � Asymmetric hypertrophy of basal interventricular septum or apex � Wall segment > 15 mm at end-diastole (> 25 mm with HTN) � SAM of the MV on cine imaging � Patchy or diffuse midmyocardial DCE Myocarditis/myopericarditis � Global or regional HK � ± Pericardial effusion � Midmyocardial or epicardial DCE Sarcoidosis � Patchy uptake of DCE � Global or regional WMA in noncoronary distribution � Focal wall thickening (acute) or wall thinning (chronic) Amyloidosis � Diffusely increased myocardial wall thickening � Biatrial enlargement � Diffuse subendocardial (but can have transmural) DCE LV noncompaction � Increased ratio of noncompacted to compacted myocardium > 2.2 in end-diastole � Involvement of > 2 segments apical to papillary muscles � NC mass of LV > 20–25% total LV mass � NC mass > 15 g/m � LV crypt thrombus Arrhythmogenic RV cardiomyopathy � Excessive mural fat content, particularly within the RV (ARVC) � Regional RV WMA � RV aneurysm 2 2 � RV dilation (EDV > 110 mL/m males/> 100 mL/m females) � RV systolic dysfunction (RVEF < 40%) Stress-induced cardiomyopathy � Hyperdynamic basal wall segments (Takotsubo) � Akinetic/dyskinetic apical segments � Absence of DCE (i.e., no evidence of infarct) � SAM List of the most commonly encountered cardiomyopathies and their correlating findings on cardiac computed tomography (CCT) MV mitral valve, LVNC left ventricular noncompaction, CAD coronary artery disease, HTN hypertension, SAM systolic anterior motion, DCE delayed contrast enhancement, WMAwall motion abnormality, NC noncompacted, LV left ventricle, RV right ventricle, EDV end-diastolic volume, RVEF right ventricular ejection fraction Future Applications imaging, a well-validated TTE for the early detection of chemotherapy-induced cardiotoxicity, can also be calculated While the utility of DE images has been discussed as it relates on CCT using the velocity gradients between two points in the to infarct detection in ischemic heart disease, iodine mapping myocardium with comparable accuracy to that of TTE . with single- or dual-energy CT can also be employed in the assessment of other cardiomyopathies where epicardial and midmyocardial scar patterns are currently observed on CMR Conclusion exclusively. CCT-based estimation of extracellular volume (ECV) by CCT may become a useful diagnostic and prognos- CCT in the form of CTP, particularly when combined with tic marker of myocardial remodeling similar to that observed CCTA, is a powerful tool in the assessment of ischemic with T1 mapping by CMR [111–113]. Strain or deformation heart disease and, with newer generation scanner Curr Cardiovasc Imaging Rep (2018) 11:16 Page 11 of 16 16 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appro- priate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. References Papers of particular interest, published recently, have been highlighted as: � Of importance �� Of major importance 1. 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Current Cardiovascular Imaging Reports
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Published: Jun 2, 2018