Multisclice CT in combination with functional imaging for CAD Prof. Juhani Knuuti, MD, FESC Turku University Hospital and University of Turku Turku, Finland MSCT and functional imaging for CAD Practical aspects of cardiac CT Technical aspects Radiation issues Patient preparation and protocols Pittfalls Clinical imaging methods for CAD The rationale of combining anatomy and function imaging techniques Quantification of myocardial perfusion Spatial Resolution Temporal Resolution 2-slice 4-slice 16-slice 64-slice 0.5mm Time required to acquire sufficient data to reconstruct a single image slice Depends primarily on gantry rotation time and reconstruction method To improve temporal resolution: speed of gantry rotation Reconstruct data acquired from less than a full gantry rotation Increases in gantry rotation speed are limited by the physical size of the components and the substantial centrifugal forces that result. Temporal resolution = ½ of the rotation time 250 Single versus Dual Source CT 500 ms 1 165 330 ms 1 1
Reconstruction Method ECG Gating R 100% R Half-scan Step 10% 25% 65% 95% Multisegment ~ Systole ~ End-Diastole Methods of ECG Gating ECG Gating Retrospective Gating Retrospective Gating with Tube Current Modulation Prospective Gating 65% 55% 95% Radiation Dose Background Radiation exposure Standard Chest X-Ray Diagnostic Angiography Percutaneous Coronary Intervention Technetium MPS PET Perfusion imaging CT Coronary Angiography ~3mSv/yr ~0.1mSv 7 msv 5-40mSv 10mSv 1-2 msv 1-30mSv Methods for Dose Reduction Tailor scan range for each patient Prospective gating if possible Tube current modulation ECG-correlated ma pulsing Body size Prospective step-and-shoot protocols Adjust tube voltage according to body weight Iterative reconstruction 2
Before arrival of the patient Preparation of the patients 1 Clinical history Indications and contraindications Serum-Creatinine (< 3 mo) Sinus rhythm or regular rhythm (pacing) Metformin medication pause Ask upon arrival Medication (beta-blockers, Ca-blockers and metformin) Allergies, asthma, contrast reactions Other diseases (especially those having impact on kidneys) Preparation of patients 2 Preparation time usually about 20 min iv cannule (G18) Careful information Lessens anxiousness (lowers HR) Rehearse breath hold (16 MDCT 15-20 sec, 64 MDCT 5-10 sec) and monitor HR response Preparation of patients 3 Blood pressure Continuous ECG monitoring Iv metoprolol 5 mg x 1-4 (6) (slow 2 min bolus), iv verapamiili (slow bolus ad 5-10 mg) if metoprolol contraindicated do not combine! (ivabradine?) Optimal HR < 60/min Isosorbidnitrate (Dinit R ) spray x 1 4-5 min before scan If necessary small dose (1-2 mg) diatsepam iv Contrast Our Contrast Protocol (300) 350 400 mgi/ml iodine 4-5+ ml/s High iodine concentration better contrast NaCl-flush recommended (dual head injector) Patient Weight <60 kg 60-90 kg >90 kg Amount of Contrast (ml, 400 mgi/ml) 60 ml 1 ml/kg 90 ml Rate (ml/s) 4 ml/s 4.5 ml/s 5 ml/s + NaCl flush 3
Our Contrast Protocol II Our Imaging Parameters (GE VCT 64-slice) Patient Weight Amount of Contrast (ml, 350 mgi/ml) Rate (ml/s) Pt size kv mas <60 kg 60-90 kg >90 kg 75 ml 80-90 ml 95 ml 5 ml/s 5 ml/s 5 ml/s Very small (80)-100 450 Small 100-120 450-600 Medium 120 600-750 Large -XL 120 ( 140) 750 + NaCl flush Scan Procedure: Bolus Tracking HU Contrast injection 60-100 ml Iomeron 400 @ 5 ml/s 150 Transition 100 50 0 0 sec 4
Optimising Images in Obese Patients Increase tube voltage and current tube voltage = X-ray photon energy = beam penetration tube current = beam intensity Both these changes increase signal at detectors ECG-gated dose modulation Tube current is increased in specified portions of the R-R interval Significantly reduces overall radiation dose when gating retrospectively and should be employed in overweight patients to compensate for increasing tube current/voltage Use higher strength contrast agent (370 or 400mg/ml) or higher flow rate (7ml/s) Optimising Images in Obese Patients Heart Rate Control Effects of Ectopic Beats HR 49 HR 67 HR 82 Flohr T et al. Herz. 2003 Feb;28(1):7-19. Effects of Coronary Calcium MSCT Stent Imaging Patent Intima Hyperplasia Occluded 5
Experience and the accuracy 1a (patients 1-47) 1b (48-94) 2a (95-151) 2b (152-207) Ovrehus KA et al J Cardiovasc Comput Tomogr. 2010 May-Jun;4(3):186-94. Summary Scan quality is reduced in very heavy patients Temporal resolution requirements necessitate -blockade Contra-indicated in asthma and heart block without pacemaker Assignment of data to R-R intervals is difficult if heart rhythm is irregular Atrial fibrillation Regular ectopic beats Positive predictive value is reduced in the presence of large quantities of calcium CCT is therefore less useful as a primary test in people where high calcium scores are expected Detection of CAD Noninvasive imaging vs obstructive CAD in ICA Patient based analysis 98 100 90 80 70 60 % 50 40 30 20 10 0 Sensitivity Specificity Ex ECG Stress Echo SPECT CMR PET MSCT 2010 Guidelines (Myocardial revascularization) Adapted from Beller GA PET Paradigm shift 1: From diagnosis to guidance of therapy Anatomy (Obstructive CAD) Flow-Limiting (Perfusion, FFR) Optimal Medical Treatment Complete Functional Revascularization and optimal medical treatment Noninvasive function: Perfusion, WMA Hachamovitch Circulation 2003;107:2900 COURAGE NEJM 2007;356:1503 COURAGE Circulation 2008;117:1283 Invasive function: FFR DEFER JACC 2007;49:2105 FAME NEJM 2009;360:213 FAME JACC 2010;56:177 Anatomical and functional imaging of coronary artery disease Anatomical imaging Invasive coronary angiography (+IVUS, OCT) Coronary Calcium Coronary CT angiography Functional imaging Nuclear imaging (SPECT, PET) Stress echocardiography CMR (FFR, invasive pressure gradient) 6
Pressure-derived FFR Invasive Imaging 1.0 0.8 0.6 0.4 0.2 N = 2334 0.0 0 20 40 60 80 100 Angiographic Diameter Stenosis (%) Cardiac CTA + PET perfusion protocol: NEW Scouts Calcium score CTA CTAC PET WA Stress perfusion Adenosine 0 5 10 15 20 25 30 Time (min) CT scan PET scan Tracer injection Contrast injection Radiation dose CTA: 3-5 msv PET: 1 msv Wijns, de Bruyne, Vanhoenacker, JNC 2007;93:856-61 Functional consequences of stenoses by PET/CT LAD Multivessel disease: What is the culprit lesion? Case: stenoses in all major vessels; RCA is culprit RCA LCX LAD D1 LAD D1, Finland Multivessel disease: What is the culprit lesion? LAD RCA C E Challenges and solutions of ischemia imaging D 3.5 0 ml/g/min FFR=0.94 FFR=0.54 F FFR=0.63 Challenge Solution LM disease Balanced 3 vessel disease Multivessel disease Anatomical location Non-ischemic CAD Microvascular disease / D1 7
noninvasive (PET/CT) vs. invasive (ICA + FFR) Sensitivity Specificity PPV (%) NPV (%) Accuracy (%) MDCT 75 Figure 95 3: Vessel 76 Analysis 94 against 91 ICA +FFR PET 94 93 77 98 93 MDCT-PET hybrid 95 99 96 99 98 100 Vessel analysis in patients with intermediate likelihood of CAD, N=107 percentage 90 80 70 60 50 40 30 20 10 0 PPV (%) NPV (%) Accuracy (%) MDCT 76 94 91 PET 77 98 93 MDCT-PET hybrid 96 99 98 MDCT PET MDCT-PET hybrid Prognosis and combined MDCT and perfusion imaging Kajander et al Circulation 2010 van Werkhoven JM, et al J Am Coll Cardiol. 2009 Feb 17;53(7):623-32. Prognostic value of hybrid imaging Impact of hybrid imaging on downstream resource utilization 1.0 Normal 100% p<0.001 96% 86% Survival Free of MACE 0.8 0.6 0.4 0.2 Log-rank p<0.001 Unmatched Matched Revascularisations 80% 60% 40% 20% 45% 39% NEJM 2010 USA N=400 000 36% GER N=840 000 0.0 0.0 1.0 2.0 3.0 4.0 Follow-up (Years) 0% CATH rate CAD yield Per CATH REVASC Per CATH 302 274 196 117 26 Eur Heart J 2011;32:1465-71 Eur Heart J 2011 Jul 30. Paradigm shift 2: From ischemic to CAD cascade Preclinical atherosclerosis Non-obstructive CAD hypoperfusion MDCT findings in patients with normal SPECT perfusion imaging result Myocardial perfusion metabolic alterations diastolic dysfunction systolic dysfunction ECG-Changes angina Signs of ischaemia Werkhoven JM, et al Am J Cardiol. 2008 Jan 1;101(1):40-5. 8
Concerns on sequential / hybrid imaging for CAD Challenges and solutions of ishchemia imaging Sequential: Complicated for patients : Logistic challenges Higher work load Non-standardized image analysis Higher radiation burden Less evidence Cost-effectiveness Challenge LM disease Balanced 3 vessel disease Multivessel disease Anatomical location Non-ischemic CAD Microvascular disease Solution Quantification Quantification Quantification/ Absolute quantification vs relative analysis in patients with multi-vessel disease 100 % 90 % 80 % 70 % 60 % 50 % 40 % 30 % 20 % 10 % 0 % PPV NPV acc absolute relative 106 patients with 30-70% pretest likelihood of CAD Quantitative hybrid PET/CT imaging vs. invasive angiography with FFR Absolute flow is as good as flow reserve! Joutsiniemi et al (Circ Imaging) Kajander S, et al 2008 Limitations CTA helps in identifying potential stenoses that can be then visualised using coronary TTE If no anatomical information is available CTA (62% diam. stenosis) Color-Doppler view Flow velocity profiles Maximal (2.1 m/s) Patients with heart failure Patients with advanced atherosclerosis but no epicardial obstructive disease Microvascular disease Ao Ao Pre-stenotic (0.3 m/s) Case 0046 Joutsiniemi et al EHJ Cardiovascular Imaging 2012 9
CTA + CMR PERFUSION Quantification of regional (LAD) myocardial perfusion by stress dynamic perfusion CT Rest Maximal vasodilatation 25% CBF reduction CT MBF: 104 ml/100ml/s FFR: 1.0 CT MBF: 236 ml/100ml/s FFR: 1.0 CT MBF: 173 ml/100ml/s FFR: 0.83 50% CBF reduction 75% CBF reduction CT MBF: 128 ml/100ml/s FFR: 0.55 CT MBF: 101 ml/100ml/s FFR: 0.50 Cardiac hybrid imaging Combination of anatomical and functional imaging Leads more accurate diagnosis of CAD Allows better guidance of CAD therapy Allows detection of non-obstructive CAD Multiple options for combinations CT + SPECT CT + PET CT + CMR CT+ CT perfusion PET + MRI Quantification of perfusion have additional value More evidence warranted especially in different diseases and patient subgroups 10