Myocardial Regions Of Interest Research Articles

Abstract 12931: Myocardial Regeneration in End-stage Heart Failure After Left Ventricular Unloading

Introduction: Left Ventricular Assist Devices (LVAD) decrease cardiac mechanical work and metabolic demand and may decrease cardiomyocyte oxidative stress, followed by cell cycle re-entry and cell regeneration. We tested whether LVAD long-term support is associated with myocardial regeneration. Methods: Viability fluorodeoxyglucose (18FDG) - positron-emission tomography scans were performed >3 months after LVAD implantation and every 6 months thereafter. 4 patients aged 18-70 with end-stage non-ischemic (NICM, n=3) or ischemic cardiomyopathy (ICM, n=1) were included. Low metabolic activity myocardial regions of interest (ROI) at <15th percentile of relative 18FDG signal intensity were identified on the baseline scan. Global signal and co-registered low-intensity ROIs were analyzed on subsequent scans vs. baseline. Results: LV ejection fraction ranged 0-35% at baseline. Two patients (LVAD speed 2660 rotations per minute - RPM, output 3.4-4.1 and 5.6-5.9 liters per minute (LPM), respectively) underwent 2 scans before cardiac transplantation, exhibiting borderline increased global signal (1-4%) and significantly increased 18FDG signal in the baseline low-intensity ROI on the follow-up scan (67.7, 75.7%). The other 2 patients (LVAD parameters: 5600 RPM/ 4.6-5.8 LPM; 9200 RPM/ 4.3-4.8 LPM) exhibited decreased global 18FDG signal (10-16%) and increased signal in the co-registered baseline low-intensity ROIs (1.7-21.5%) (Figure). Conclusions: LVAD long-term support is associated with a global decrease in myocardial 18FDG uptake signal over time, and with increased viability signal in baseline low-intensity ROIs, suggestive of myocardial regeneration in metabolically inactive regions. Future research is required to identify patient subgroups that are most likely to exhibit high regeneration potential upon long-term LVAD support.

T1-Mapping and extracellular volume estimates in pediatric subjects with Duchenne muscular dystrophy and healthy controls at 3T

BackgroundCardiovascular disease is the leading cause of death in patients with Duchenne muscular dystrophy (DMD)—a fatal X-linked genetic disorder. Late gadolinium enhancement (LGE) imaging is the current gold standard for detecting myocardial tissue remodeling, but it is often a late finding. Current research aims to investigate cardiovascular magnetic resonance (CMR) biomarkers, including native (pre-contrast) T1 and extracellular volume (ECV) to evaluate the early on-set of microstructural remodeling and to grade disease severity. To date, native T1 measurements in DMD have been reported predominantly at 1.5T. This study uses 3T CMR: (1) to characterize global and regional myocardial pre-contrast T1 differences between healthy controls and LGE + and LGE− boys with DMD; and (2) to report global and regional myocardial post-contrast T1 values and myocardial ECV estimates in boys with DMD, and (3) to identify left ventricular (LV) T1-mapping biomarkers capable of distinguishing between healthy controls and boys with DMD and detecting LGE status in DMD.MethodsBoys with DMD (N = 28, 13.2 ± 3.1 years) and healthy age-matched boys (N = 20, 13.4 ± 3.1 years) were prospectively enrolled and underwent a 3T CMR exam including standard functional imaging and T1 mapping using a modified Look-Locker inversion recovery (MOLLI) sequence. Pre-contrast T1 mapping was performed on all boys, but contrast was administered only to boys with DMD for post-contrast T1 and ECV mapping. Global and segmental myocardial regions of interest were contoured on mid LV T1 and ECV maps. ROI measurements were compared for pre-contrast myocardial T1 between boys with DMD and healthy controls, and for post-contrast myocardial T1 and ECV between LGE + and LGE− boys with DMD using a Wilcoxon rank-sum test. Results are reported as median and interquartile range (IQR). p-Values < 0.05 were considered significant. Receiver Operating Characteristic analysis was used to evaluate a binomial logistic classifier incorporating T1 mapping and LV function parameters in the tasks of distinguishing between healthy controls and boys with DMD, and detecting LGE status in DMD. The area under the curve is reported.ResultsBoys with DMD had significantly increased global native T1 [1332 (60) ms vs. 1289 (56) ms; p = 0.004] and increased within-slice standard deviation (SD) [100 (57) ms vs. 74 (27) ms; p = 0.001] compared to healthy controls. LGE− boys with DMD also demonstrated significantly increased lateral wall native T1 [1322 (68) ms vs. 1277 (58) ms; p = 0.001] compared to healthy controls. LGE + boys with DMD had decreased global myocardial post-contrast T1 [565 (113) ms vs 635 (126) ms; p = 0.04] and increased global myocardial ECV [32 (8) % vs. 28 (4) %; p = 0.02] compared to LGE− boys. In all classification tasks, T1-mapping biomarkers outperformed a conventional biomarker, LV ejection fraction. ECV was the best performing biomarker in the task of predicting LGE status (AUC = 0.95).ConclusionsBoys with DMD exhibit elevated native T1 compared to healthy, sex- and age-matched controls, even in the absence of LGE. Post-contrast T1 and ECV estimates from 3T CMR are also reported here for pediatric patients with DMD for the first time and can distinguish between LGE + from LGE− boys. In all classification tasks, T1-mapping biomarkers outperform a conventional biomarker, LVEF.

Usefulness Of Two-Dimensional Echo Strain In Evaluation Of Cardiac Function In Elite Athletes

PURPOSE: Cardiovascular adaptation to sport training is influenced by many factors, including the intensity and the kind of sport practiced. The “Morganroth hypothesis” asserted that a static exercise characterized by a pressure load and dynamic (isotonic) exercise which involves a volume load to the heart lead to different myocardial adaptation patterns. More recent studies revisited this hypothesis, showing that left ventricular (LV) remodelling observed in both resistance and endurance trained athletes, presented similar aspects. Although morphological modifications secondary to exercise have been largely studied, less is known on myocardial systolic function in LV remodeling patterns in different elite athletes. Two-dimensional strain analysis allows a complete study of the contractile function in different myocardial regions of interest in left and right ventricle. In this study we aim to underline possible differences in contractile myocardial function with strain analysis in two groups of elite athletes, trained with different loads and playing different sports (football and cyclism). METHODS: We enrolled 47 male athletes: 23 football players and 24 cyclists, belonging to same football or cyclism team (mean age in both groups 18±3 years old). The athletes were evaluated with echocardiography at the beginning of the sports season. We assessed LV contractile function using speckle-tracking echocardiographic global longitudinal strain (GLS) and global circumferential strain (GCS). We also analysed right ventricular function by strain echocardiography. RESULTS: Cyclists showed a significantly augmented indexed LV mass and TAPSE. No significant differences were found in GLS data between the two groups (23.4±0.02 in football players and 24.1±0.02 in cyclists), whereas a significantly higher GCS was found in cyclists compared to football players (31.2±0.04 and 27.2±0.05 respectively, p< 0.005). The cyclist group showed a significant increase in right ventricular strain compared to football players (26.3±0.04 and 23.2±0.04, respectively, p< 0.05). CONCLUSIONS: Our preliminary data suggest that a dynamic exercise, which involves a volume load, like cyclism, lead to a sensible increase in systolic function in elite athletes especially in right ventricle contractility.

MR-based motion correction for cardiac PET parametric imaging: a simulation study

BackgroundBoth cardiac and respiratory motions bias the kinetic parameters measured by dynamic PET. The aim of this study was to perform a realistic positron emission tomography-magnetic resonance (PET-MR) simulation study using 4D XCAT to evaluate the impact of MR-based motion correction on the estimation of PET myocardial kinetic parameters using PET-MR. Dynamic activity distributions were obtained based on a one-tissue compartment model with realistic kinetic parameters and an arterial input function. Realistic proton density/T1/T2 values were also defined for the MRI simulation. Two types of motion patterns, cardiac motion only (CM) and both cardiac and respiratory motions (CRM), were generated. PET sinograms were obtained by the projection of the activity distributions. PET image for each time frame was obtained using static (ST), gated (GA), non-motion-corrected (NMC), and motion-corrected (MC) methods. Voxel-wise unweighted least squares fitting of the dynamic PET data was then performed to obtain K1 values for each study. For each study, the mean and standard deviation of K1 values were computed for four regions of interest in the myocardium across 25 noise realizations.ResultsBoth cardiac and respiratory motions introduce blurring in the PET parametric images if the motion is not corrected. Conventional cardiac gating is limited by high noise level on parametric images. Dual cardiac and respiratory gating further increases the noise level. In contrast to GA, the MR-based MC method reduces motion blurring in parametric images without increasing noise level. It also improves the myocardial defect delineation as compared to NMC method. Finally, the MR-based MC method yields lower bias and variance in K1 values than NMC and GA, respectively. The reductions of K1 bias by MR-based MC are 7.7, 5.1, 15.7, and 29.9% in four selected 0.18-mL myocardial regions of interest, respectively, as compared to NMC for CRM. MR-based MC yields 85.9, 75.3, 71.8, and 95.2% less K1 standard deviation in the four regions, respectively, as compared to GA for CRM.ConclusionsThis simulation study suggests that the MR-based motion-correction method using PET-MR greatly reduces motion blurring on parametric images and yields less K1 bias without increasing noise level.

Remote Zone Extracellular Volume and Left Ventricular Remodeling in Survivors of ST-Elevation Myocardial Infarction

The natural history and pathophysiological significance of tissue remodeling in the myocardial remote zone after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. Extracellular volume (ECV) in myocardial regions of interest can now be measured with cardiac magnetic resonance imaging. Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [British Heart Foundation Magnetic Resonance Imaging in Acute ST-Segment Elevation Myocardial Infarction study]). Cardiac magnetic resonance was performed at 1.5 Tesla at 2 days and 6 months post STEMI. T1 modified Look-Locker inversion recovery mapping was performed before and 15 minutes after contrast (0.15 mmol/kg gadoterate meglumine) in 140 patients at 2 days post STEMI (mean age: 59 years, 76% male) and in 131 patients at 6 months post STEMI. Remote zone ECV was lower than infarct zone ECV (25.6±2.8% versus 51.4±8.9%; P<0.001). In multivariable regression, left ventricular ejection fraction was inversely associated with remote zone ECV (P<0.001), and diabetes mellitus was positively associated with remote zone ECV (P=0.010). No ST-segment resolution (P=0.034) and extent of ischemic area at risk (P<0.001) were multivariable associates of the change in remote zone ECV at 6 months (ΔECV). ΔECV was a multivariable associate of the change in left ventricular end-diastolic volume at 6 months (regression coefficient [95% confidence interval]: 1.43 (0.10-2.76); P=0.036). ΔECV is implicated in the pathophysiology of left ventricular remodeling post STEMI, but because the effect size is small, ΔECV has limited use as a clinical biomarker of remodeling. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02072850.

How well do individual first pass perfusion images correlate with fully quantitative myocardial blood flow pixel maps?

Methods 27 subjects (17 male; age 62 ± 11 years) with coronary artery disease as defined by quantitative coronary angiography were included in this study. Greater than 70% luminal coronary stenosis of the major epicardial coronaries was present in 2/3 of the subjects. Perfusion imaging was performed using a saturation recovery steadystate free precession dual-sequence method at 1.5 T during Regadenoson vasodilator stress and at rest, using 0.05 mmol/kg Gadolinium-DTPA. Pixel-wise MBF maps were calculated from a mid-ventricular motion-corrected image series. Myocardial regions of interest were manually traced on the perfusion image series to restrict analysis to the myocardium. The MBF pixel values were then correlated with individual perfusion image signal intensities on a pixel-by-pixel basis for each perfusion image in the series (Pearson’s correlation coefficient).

Prognostic significance of infarct core pathology revealed by quantitative non-contrast in comparison with contrast cardiac magnetic resonance imaging in reperfused ST-elevation myocardial infarction survivors.

AimsTo assess the prognostic significance of infarct core tissue characteristics using cardiac magnetic resonance (CMR) imaging in survivors of acute ST-elevation myocardial infarction (STEMI).Methods and resultsWe performed an observational prospective single centre cohort study in 300 reperfused STEMI patients (mean ± SD age 59 ± 12 years, 74% male) who underwent CMR 2 days and 6 months post-myocardial infarction (n = 267). Native T1 was measured in myocardial regions of interest (n = 288). Adverse remodelling was defined as an increase in left ventricular (LV) end-diastolic volume ≥20% at 6 months. All-cause death or first heart failure hospitalization was a pre-specified outcome that was assessed during follow-up (median duration 845 days). One hundred and sixty (56%) patients had a hypo-intense infarct core disclosed by native T1. In multivariable regression, infarct core native T1 was inversely associated with adverse remodelling [odds ratio (95% confidence interval (CI)] per 10 ms reduction in native T1: 0.91 (0.82, 0.00); P = 0.061). Thirty (10.4%) of 288 patients died or experienced a heart failure event and 13 of these events occurred post-discharge. Native T1 values (ms) within the hypo-intense infarct core (n = 160 STEMI patients) were inversely associated with the risk of all-cause death or first hospitalization for heart failure post-discharge (for a 10 ms increase in native T1: hazard ratio 0.730, 95% CI 0.617, 0.863; P < 0.001) including after adjustment for left ventricular ejection fraction, infarct core T2 and myocardial haemorrhage. The prognostic results for microvascular obstruction were similar.ConclusionInfarct core native T1 represents a novel non-contrast CMR biomarker with potential for infarct characterization and prognostication in STEMI survivors. Confirmatory studies are warranted.ClinicalTrials.gov identifierNCT02072850.

Dynamic Myocardial Perfusion in a Porcine Balloon-induced Ischemia Model using a Prototype Spectral Detector CT.

Myocardial CT perfusion (CTP) imaging is an application that should greatly benefit from spectral CT through the significant reduction of beam hardening (BH) artifacts using mono-energetic (monoE) image reconstructions. We used a prototype spectral detector CT (SDCT) scanner (Philips Healthcare) and developed advanced processing tools (registration, segmentation, and deconvolution-based flow estimation) for quantitative myocardial CTP in a porcine ischemia model with different degrees of coronary occlusion using a balloon catheter. The occlusion severity was adjusted with fractional flow reserve (FFR) measurements. The SDCT scanner is a single source, dual-layer detector system, which allows simultaneous acquisitions of low and high energy projections, hence enabling accurate projection-based material decomposition and effective reduction of BH-artifacts. In addition, the SDCT scanner eliminates partial scan artifacts with fast (0.27s), full gantry rotation acquisitions. We acquired CTP data under different hemodynamic conditions and reconstructed conventional 120kVp images and projection-based monoenergetic (monoE) images for energies ranging from 55keV-to-120keV. We computed and compared myocardial blood flow (MBF) between different reconstructions. With balloon completely deflated (FFR=1), we compared the mean attenuation in a myocardial region of interest before iodine arrival and at peak iodine enhancement in the left ventricle (LV), and we found that monoE images at 70keV effectively minimized the difference in attenuation, due to BH, to less than 1 HU compared to 14 HU with conventional 120kVp images. Flow maps under baseline condition (FFR=1) were more uniform throughout the myocardial wall at 70keV, whereas with 120kVp data about 12% reduction in blood flow was noticed on BH-hypoattenuated areas compared to other myocardial regions. We compared MBF maps at different keVs under an ischemic condition (FFR < 0.7), and we found that flow-contrast-to-noise-ratio (CNR f ) between LAD ischemic and remote healthy territories attains its maximum (2.87 ± 0.7) at 70keV. As energies diverge from 70keV, we noticed a steady decrease in CNRf and an overestimation of mean-MBF. Flow overestimation was also noticed for conventional 120kVp images in different myocardial regions.

Semi-quantitative assessment of resting perfusion in chronic myocardial infarction

Background Based on observations from cardiovascular magnetic resonance (CMR) imaging, it is not clear whether chronic myocardial infarction (MI) is associated with abnormal perfusion at rest. Our aim was to investigate this question using semi-quantitative analysis of resting myocardial perfusion to compare areas of infarct and remote myocardium in patients with known coronary anatomy. Methods We identified 19 patients who underwent regadenoson stress CMR (1.5T, Philips), had MI confirmed by late gadolinium enhancement (LGE), and underwent invasive coronary angiography within 6 months of CMR. Stress perfusion images were obtained during first pass of Gadolinium contrast agent one minute after regadenoson (0.4mg IV bolus) injection, and followed by reversal with aminophylline (75-125 mg), rest perfusion and late gadolinium enhancement (LGE) imaging 10-15 minutes later. Resting time-intensity curves were generated for a region of interest (ROI) in the area of MI, remote myocardium, and blood pool (Medis). Myocardial curves were used to obtain maximal up-slopes and normalized by the blood pool. Up-slopes were compared between the infarcted and remote myocardial ROIs. Results There was no significant difference between the slopes in the infarcted and remote myocardium (0.31 ± 0.17 vs 0.32 ± 0.18 1/s) irrespective of presence of significant stenosis

Abstract 17328: Ultrasmall Supraparamagnetic Particles of Iron Oxide-enhanced Magnetic Resonance Imaging in the Assessment of Cellular Inflammation after Myocardial Infarction

Introduction: Excessive inflammation after myocardial infarction (MI) can be detrimental to the recovery of cardiac function. Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect myocardial cellular inflammation after MI. We aimed to determine the time course and duration of USPIO-enhancement following acute MI. Methods: Twenty-one patients with acute MI were studied in the 3-month period following acute MI. Repeated T2*-weighted 3T MRI was performed throughout and 24 h after USPIO (ferumoxytol, 4 mg/kg) administration at 4±3, 12±2, 21±4 and 90±9 days. Myocardial regions of interest (ROIs) were drawn and categorised into infarct and non-infarct regions by the presence or absence of late gadolinium enhancement (LGE). R2* values within ROIs were determined to assess the time course and duration of uptake and clearance of USPIO. Results: Following single-dose USPIO administration 2-7 days after acute MI, USPIO uptake is demonstrable at 24 h (p&lt;0.0001) and is cleared within 4-8 days (Figure 1a). Increased USPIO uptake is seen in the infarct region at days 2-7 (p&lt;0.0001), and days 10-14 (p&lt;0.05) compared to non-infarcted myocardium (Figure 1b). Conclusions: For the first time, we have shown USPIO-enhanced MRI can detect and quantify infarct-related cellular inflammation in the first 2 weeks following acute MI.

Incremental prognostic value of 99mTc-tetrofosmin early poststress pulmonary uptake. Determination of the optimal cut-off value

To evaluate the incremental prognostic value of (99m)Tc-tetrofosmin early poststress lung/heart ratio (eLHR) and to assess the optimal cut-off value. We studied 503 patients (aged 61.3 years/SD = 8.6 years, 302 men) with stress/rest (99m)Tc-tetrofosmin myocardial gated-single photon emission computed tomography and coronary angiography. To evaluate myocardial ischemia, the summed stress score, summed rest score, and summed difference score indices were calculated. For the eLHR calculation, an anterior image was acquired 4-6 min after radiotracer injection at stress; eLHR was defined as the mean counts/pixel in the lung region of interest divided by the mean counts/pixel in the myocardial region of interest. The incremental prognostic value of eLHR was evaluated by a significant increase in the global χ(2) of the Cox proportional hazard model that included clinical, exercise, angiographic, and scintigraphic variables. Using the receiver operating characteristic analysis, the optimal cut-off of eLHR for the prediction of cardiac events was determined. During the follow-up period, hard cardiac events occurred in 50 (9.9%) and soft cardiac events in 61 (12.1%) patients. Receiver operating characteristic curve analysis showed that the optimal cut-off of eLHR for the prediction of cardiac events was 0.51, with a sensitivity of 78.4% and specificity of 72.2%. The area under the curve was 0.82 (95% confidence interval: 0.77-0.87). Multiple Cox regression analysis revealed that eLHR more than 0.51 (hazard ratio = 7.78; 95% confidence interval: 5.00-12.11) provided incremental prognostic value over clinical exercise testing and scintigraphic data for cardiac events. A (99m)Tc-tetrofosmin eLHR value larger than 0.51 added incremental value to other variables for the prediction of cardiac events.

Automated quantification of myocardial perfusion based on segmentation and non-rigid registration of contrast-enhanced cardiac magnetic resonance images

Quantification of myocardial perfusion from cardiac magnetic resonance (CMR) images relies on manual tracing of myocardial regions of interest (ROIs) and their repositioning frame-by-frame throughout the contrast-enhanced image sequence. Additionally, out-of-plane motion due to patient’s respiration frequently requires that myocardial ROIs to be redrawn.This tedious and potentially inaccurate methodology hinders widespread clinical use of imaging-based quantification of myocardial perfusion.

Intraoperative CD133+ cell transplantation during coronary artery bypass grafting in ischemic cardiomyopathy

If traditional treatment of coronary artery disease has failed, intramyocardial transplantation of CD133+ stem cells with the potential to improve myocardial function is an alternative approach to treating ischemic cardiomyopathy. The INSTEM trial aims at evaluating safety and feasibility of isolation and subsequent intramyocardial transplantation of CD133+ cells in combination with coronary artery bypass grafting (CABG). Patients suffering from severe ischemic cardiomyopathy (ejection fraction ≫15% and ≪35%) are enrolled in this trial. Bone marrow is harvested from the iliac crest and CD133+ cells are purified up to 99%. The myocardial region of interest is pre-treated by transmyocardial laser revascularization in order to trigger homing of transplanted cells. Autologous bone marrow CD133+ cells (up to 30×10(6)cells) are injected into predefined myocardial regions. Cardiac function prior to as well as three, six and 12months after cell transplantation is assessed by echocardiography. Neither operative mortalities nor any cardiac deaths during follow-up occurred. Left ventricular ejection fraction improved from 25%±5% preoperatively to 40%±8% after six months. Our method of intraoperative CD133+ cell isolation while performing CABG and subsequent transmyocardial cell transplantation is feasible and safe. Although the follow-up has not yet been completed we propose this procedure to be a promising causal therapy of severe ischemic cardiomyopathy.

Feasibility of automated frame-by-frame myocardial segmentation as a basis for quantification of first-pass perfusion images

Introduction Quantification of first-pass myocardial perfusion from cardiac magnetic resonance (CMR) images relies on the definition of myocardial regions of interest (ROI). This is usually achieved by manually drawing ROIs in one frame and then adjusting their position on subsequent frames. This methodology is tedious and potentially inaccurate. We recently developed a technique based on image noise density distribution for automated dynamic endocardial border detection as a basis for quantification of left ventricular size and function.

Long-term prognostic value of early poststress 99mTc-tetrofosmin lung uptake during exercise (SPECT) myocardial perfusion imaging

The aim of this study was to determine the long-term prognostic value of early poststress lung/heart ratio (LHR) of (99m)Tc-tetrofosmin radioactivity. We studied 276 patients (aged 62.2 + or - 8.9 years, 168 men) with stress/rest (99m)Tc-tetrofosmin myocardial gated-SPECT and coronary angiography. To evaluate myocardial ischaemia, we calculated the summed stress score, summed rest score and summed difference score indices. For the eLHR calculation, an anterior image was acquired, 4-6 min after radiotracer injection at stress (eLHR was defined as mean counts per pixel in the lung region of interest divided by the mean counts per pixel in the myocardial region of interest). Cardiovascular death and nonfatal myocardial infarction were considered as hard cardiac events, and late revascularization procedures as soft cardiac events. The Cox proportional hazards model in a stepwise method was used to determine the independent predictors for hard and soft cardiac events. During the follow-up period hard cardiac events occurred in 28 patients (10.1%) and soft cardiac events in 32 patients (11.6%). Implying multiple Cox regression analysis, eLHR was found to be a significant independent predictor for both soft and hard cardiac events. The hazard ratio (for a 0.1 unit increase) was 4.41 (95% CI 1.52-12.73, p=0.006) for soft cardiac events and 4.22 (95% CI 2.07-8.62, p<0.001) for hard cardiac events. The other significant prognostic factors were use of beta-blockers, the summed stress score and the use of nitrates for soft events, and exercise duration and the summed stress score for hard cardiac events. Early poststress (99m)Tc-tetrofosmin LHR has an independent and powerful value in predicting hard and soft cardiac events.

Semi-automated analysis of dynamic changes in myocardial contrast from real-time three-dimensional echocardiographic images as a basis for volumetric quantification of myocardial perfusion

Despite the potential of real-time three-dimensional (3D) echocardiography (RT3DE) to assess myocardial perfusion, there is no quantification method available for perfusion analysis from RT3DE images. Such method would require 3D regions of interest (ROI) to be defined and adjusted frame-by-frame to compensate for cardiac translation and deformation. Our aims were to develop and test a technique for automated identification of 3D myocardial ROI suitable for translation-free quantification of myocardial videointensity over time, MVI(t), from contrast-enhanced RT3DE images. Twelve transthoracic RT3DE (Philips) data sets obtained in pigs during transition from no contrast to steady-state enhancement (Definity) were analysed using custom software. Analysis included: (i) semi-automated detection of left ventricular endo- and epicardial surfaces using level-set techniques in one frame to define a 3D myocardial ROI, (ii) rigid 3D registration to reduce translation and rotation, (iii) elastic 3D registration to compensate for deformation, and (iv) quantification of MVI(t) in the 3D ROI from the registered and non-registered data sets to assess the effectiveness of registration. For each MVI(t) curve we computed % variability during steady-state enhancement (100 x SD/mean) and goodness of fit (r2) to the indicator dilution equation MVI(t) = A[1-exp(-betat)]. Analysis of myocardial contrast throughout contrast inflow was feasible in all data sets. Three-dimensional registration improved MVI(t) curves in terms of both % variability (2.8 +/- 1.8 to 1.5 +/- 0.9%; P < 0.05) and goodness of fit (r2 from 0.79 +/- 0.2 to 0.90 +/- 0.1; P < 0.05). This is the first study to describe a new technique for semi-automated volumetric quantification of myocardial contrast from RT3DE images that includes registration and thus provides the basis for 3D measurement of myocardial perfusion.

Cardiac T2* Magnetic Resonance Imaging (MRI) in Iron Overload and Ventricular Diastolic Function.

Accumulation of iron in the heart leads to myocardial dysfunction and in severe cases heart failure. Myocardial hemosiderosis occurs in many hematological diseases treated with blood transfusions, including sickle cell anemia (SCA) and beta thalassemia (β-thal). MRI T2* can quantify myocardial iron non-invasively and can be compared to functional studies (e.g., echocardiography). Multiple MRI readers can introduce variation in the measurement. We investigated the relationship of myocardial MRI T2* with echo measurements of both systolic and diastolic function, and the variability introduced by different MRI reviewers. Patients were selected if they received ≥ 18 transfusions, or had a serum ferritin ≥ 1000 ng/mL. Study participants underwent 1.5 Tesla MRI T2* and echocardiography testing within 30 days. Echo measurements included left ventricular ejection fraction (LVEF), mitral annular tissue Doppler (TDV) e' velocity (a measure of LV diastolic function), left ventricular myocardial performance index (a measure of both systolic and diastolic function - LVMPI), and left ventricular mass index (LVMI). Regions of interest (ROI) were drawn in a homogeneous area of the intraventricular septum. Three independent reviewers, blinded to the patients' clinical status and the other 2 reviewers' results, performed the ROI analysis. Agreement among the 3 raters was assessed using interclass correlation coefficient (ICC). Echo findings were associated with heart T2* both as continuous and categorical (normal vs abnormal) variables. Forty-seven patients, median age 14 years (range 7 – 37), participated; 24 (51.1%) were female. Thirty-five (74.5%) had SCA, 8 (17%) had β-thal (major or intermedia), and 4 (8.5%) had bone marrow failure syndromes. Mean (±1SD) echo results were LVEF (±5.8) %, LVMI 86 (±20.4) g/m2, LVMPI 0.3 (±0.1), and TDV e' velocity 16.2 (±3.4) cm/sec. Only one patient had low LVEF, but 8 (17%) had high LVMPI and 20 (42%) had low TDV e' velocity. All patients had normal LVMI. The mean myocardium T2* ranged among the 3 reviewers from 27 to 33 (±6.9 to 8.7) msec. Agreement among the 3 raters had an ICC = 0.64. Median T2* values were significantly lower among patients with lower LVMI (32 versus 42 msec, p= 0.019). No other comparisons among echo and T2* results were significant. Median echo findings were compared with T2* values above and below 20 msec: lower LVMI (71 vs 89 g/m2, p=0.04), and higher LVMPI (0.48 versus 0.28, p=0.015) were found among patients with T2* < 20 msec. Mean serum ferritin was 2917 (±2239) ng/mL. Serum ferritin was significantly negatively associated with T2* values (ρ=−0.33, p=0.031). We conclude:1.Most patients had normal LV systolic function, but 42% had signs of diastolic dysfunction,2.LVMPI was associated with myocardial iron loading (T2*>20msec), suggesting diastolic dysfunction to be an early sign of myocardial dysfunction in cardiac hemosiderosis,3.Heart T2* was weakly associated with serum ferritin,4.The agreement among reviewers of the heart T2* technique was acceptable, but not high, likely reflecting technical difficulties of accurate myocardial ROI determination on “bright blood” T2* maps drawn on thin intraventricular septa.Dark blood techniques should therefore be investigated to reduce blood artifacts, potentially improving accuracy by eliminating artifacts from bright blood signals and thus reducing inter-rater variability in the ROI analysis of myocardial iron.

Early post-stress pulmonary uptake of 99mTc tetrofosmin during exercise (SPECT) myocardial perfusion imaging: Correlation with haemodynamic, perfusion and function parameters

To test the association of early post-stress lung/heart ratio (LHR) of 99mTc tetrofosmin radioactivity with gated-SPECT findings and angiographic results. We studied 158 consecutive patients, with stress/rest 99mTc tetrofosmin myocardial SPECT and coronary angiography. Rest scans were obtained as gated SPECT and the left ventricular ejection fraction and end diastolic volume were calculated. To evaluate myocardial ischaemia, we calculated the summed stress score, summed rest score and summed difference score indices. For the LHR calculation, we acquired an anterior image, 4-6 min after radiotracer injection at stress; LHR was defined as mean counts/pixel in the lung region of interest divided by the mean counts/pixel in the myocardial region of interest. An early post-stress LHR value of 0.500 was defined as the upper normal limit. The most significant correlation (P<0.001) was observed among early post-stress LHR, summed stress score and the number of stenosed vessels. The incidence of multi-vessel coronary artery disease in the subgroup of patients with increased values of early post-stress LHR, was significantly higher than in the normal group (81% vs. 42%, P<0.001). There was a significant difference (P<0.001) of the early post-stress LHR value between patients with normal coronary arteries or one-vessel disease and patients with multi-vessel disease. Early post-stress LHR was an independent predictor of multi-vessel coronary artery disease (coefficient 1.85, SD 0.16, P<0.001), with an incremental value for its identification. Our results suggest that early post-stress 99mTc tetrofosmin LHR appears to be a useful index of extensive myocardial ischaemia dysfunction and multi-vessel coronary artery disease.

Development of modified method for quantification of regional myocardial blood flow using 15O-water with PET

We have designed a new practical algorithm, which allows stable, rapid and automated quantification of regional MBF using 15O-water with PET. Methods: Thirty-six volunteers were employed in the static 15O–CO and dynamic 15O-water PET studies. To evaluate the reproducibility of the estimates, a repeat 15O-water scan was carried out. This algorithm includes a procedure for positioning a three-dimensional region of interest (ROI) of the whole myocardium and dividing it into 16 segments. Subsequently, the uniform input function was calculated using time–activity curves in the whole myocardial ROI and in the left ventricular ROI. The uniform input function allowed a simple and robust algorithm to estimate regional MBF. Estimates were compared with those by an original method. A simulation study was carried out to compare the effects of errors in PTF or Va on the MBF using the two methods. Results: The average analyzing time to define whole and 16 regional myocardial ROIs was less than 5 min. The new method yielded less deviated regional MBF than those with the traditional method. This method yielded significantly higher reproducibility of regional MBF than the original method. Our new method yielded a better correlation in the repeated measurement values of regional MBF and less variability among the regions in the myocardium than with an original theory of 15O-water technique. The simulation study demonstrated less effects of error in PTF or Va on the MBF value with the new method. Conclusions: We have developed a technique for an automated, simplified and stable algorithm to quantify regional MBF. This software is considered to be practical for clinical use in a myocardial PET study using 15O-water with high reproducibility and short processing time.

Realignment of myocardial first-pass MR perfusion images using an automatic detection of the heart-lung interface.

Magnetic resonance first-pass imaging of a bolus of contrast agent is well adapted to distinguish normal and hypoperfused areas of the myocardium. In most cases, the signal intensity-time curves in user defined regions of interest (ROI) are studied. As image acquisition is ECG-gated, the images are acquired at the same moment in the cardiac cycle, and the basic shape of the heart is similar from one view to the next. However, superficial respiratory motion can displace the heart in the short-axis plane. The aim of this study is to correct for the respiratory motion of the heart by performing an automatic realignment of the myocardial ROI based on a method tracking the movement of the lung-myocardium interface. Visual and quantitative analyses performed on 120 curves show a very good concordance between two automatic methods and the manual one.