David C. Wendell

Relationship of T2-Weighted MRI Myocardial Hyperintensity and the Ischemic Area-At-Risk

RATIONALE After acute myocardial infarction (MI), delineating the area-at-risk (AAR) is crucial for measuring how much, if any, ischemic myocardium has been salvaged. T2-weighted MRI is promoted as an excellent method to delineate the AAR. However, the evidence supporting the validity of this method to measure the AAR is indirect, and it has never been validated with direct anatomic measurements. OBJECTIVE To determine whether T2-weighted MRI delineates the AAR. METHODS AND RESULTS Twenty-one canines and 24 patients with acute MI were studied. We compared bright-blood and black-blood T2-weighted MRI with images of the AAR and MI by histopathology in canines and with MI by in vivo delayed-enhancement MRI in canines and patients. Abnormal regions on MRI and pathology were compared by (a) quantitative measurement of the transmural-extent of the abnormality and (b) picture matching of contours. We found no relationship between the transmural-extent of T2-hyperintense regions and that of the AAR (bright-blood-T2: r=0.06, P=0.69; black-blood-T2: r=0.01, P=0.97). Instead, there was a strong correlation with that of infarction (bright-blood-T2: r=0.94, P<0.0001; black-blood-T2: r=0.95, P<0.0001). Additionally, contour analysis demonstrated a fingerprint match of T2-hyperintense regions with the intricate contour of infarcted regions by delayed-enhancement MRI. Similarly, in patients there was a close correspondence between contours of T2-hyperintense and infarcted regions, and the transmural-extent of these regions were highly correlated (bright-blood-T2: r=0.82, P<0.0001; black-blood-T2: r=0.83, P<0.0001). CONCLUSION T2-weighted MRI does not depict the AAR. Accordingly, T2-weighted MRI should not be used to measure myocardial salvage, either to inform patient management decisions or to evaluate novel therapies for acute MI.

INCLUDING AORTIC VALVE MORPHOLOGY IN COMPUTATIONAL FLUID DYNAMICS SIMULATIONS: INITIAL FINDINGS AND APPLICATION TO AORTIC COARCTATION

Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality.

A coupled experimental and computational approach to quantify deleterious hemodynamics, vascular alterations, and mechanisms of long-term morbidity in response to aortic coarctation

INTRODUCTION Coarctation of the aorta (CoA) is associated with morbidity despite treatment. Although mechanisms remain elusive, abnormal hemodynamics and vascular biomechanics are implicated. We present a novel approach that facilitates quantification of coarctation-induced mechanical alterations and their impact on vascular structure and function, without genetic or confounding factors. METHODS Rabbits underwent thoracic CoA at 10weeks of age (~9 human years) to induce a 20mmHg blood pressure (BP) gradient using permanent or dissolvable suture thereby replicating untreated and corrected CoA. Computational fluid dynamics (CFD) was performed using imaging and BP data at 32weeks to quantify velocity, strain and wall shear stress (WSS) for comparison to vascular structure and function as revealed by histology and myograph results. RESULTS Systolic and mean BP was elevated in CoA compared to corrected and control rabbits leading to vascular thickening, disorganization and endothelial dysfunction proximally and distally. Corrected rabbits had less severe medial thickening, endothelial dysfunction, and stiffening limited to the proximal region despite 12weeks of normal BP (~4 human years) after the suture dissolved. WSS was elevated distally for CoA rabbits, but reduced for corrected rabbits. DISCUSSION These findings are consistent with alterations in humans. We are now poised to investigate mechanical contributions to mechanisms of morbidity in CoA using these methods.

Altered hemodynamics, endothelial function, and protein expression occur with aortic coarctation and persist after repair

Coarctation of the aorta (CoA) is associated with substantial morbidity despite treatment. Mechanically induced structural and functional vascular changes are implicated; however, their relationship with smooth muscle (SM) phenotypic expression is not fully understood. Using a clinically representative rabbit model of CoA and correction, we quantified mechanical alterations from a 20-mmHg blood pressure (BP) gradient in the thoracic aorta and related the expression of key SM contractile and focal adhesion proteins with remodeling, relaxation, and stiffness. Systolic and mean BP were elevated for CoA rabbits compared with controls leading to remodeling, stiffening, an altered force response, and endothelial dysfunction both proximally and distally. The proximal changes persisted for corrected rabbits despite >12 wk of normal BP (~4 human years). Computational fluid dynamic simulations revealed reduced wall shear stress (WSS) proximally in CoA compared with control and corrected rabbits. Distally, WSS was markedly increased in CoA rabbits due to a stenotic velocity jet, which has persistent effects as WSS was significantly reduced in corrected rabbits. Immunohistochemistry revealed significantly increased nonmuscle myosin and reduced SM myosin heavy chain expression in the proximal arteries of CoA and corrected rabbits but no differences in SM α-actin, talin, or fibronectin. These findings indicate that CoA can cause alterations in the SM phenotype contributing to structural and functional changes in the proximal arteries that accompany the mechanical stimuli of elevated BP and altered WSS. Importantly, these changes are not reversed upon BP correction and may serve as markers of disease severity, which explains the persistent morbidity observed in CoA patients.

Flow-Independent Dark-blood DeLayed Enhancement (FIDDLE): validation of a novel black blood technique for the diagnosis of myocardial infarction

Background A fundamental component of the CMR exam is contrast enhanced imaging, which is crucial for delineating diseased from normal tissue. Unfortunately, diseased tissue adjacent to vasculature often remains hidden since there is poor contrast between hyperenhanced tissue and bright blood-pool. Conventional black-blood double-IR methods are not a solution; these were not designed to function after contrast administration since they rely on the long native T1 of blood (~2s at 3T) and adequate blood flow within this time period. We introduce a novel Flow-Independent Dark-blood DeLayed Enhancement technique (FIDDLE) that allows visualization of tissue contrast-enhancement while suppressing blood-pool signal. We validate FIDDLE in an animal model of myocardial infarction (MI) and demonstrate feasibility in patients.

Comparison of T2-preparation and magnetization-transfer preparation for black blood delayed enhancement

Background A fundamental component of the CMR exam is contrast enhanced imaging, which is crucial for delineating diseased from normal tissue. Unfortunately, diseased tissue immediately adjacent to blood often is hidden since there is poor contrast between hyperenhanced tissue and bright blood. A new method recently described, Flow-Independent Dark-blood DeLayed Enhancement technique (FIDDLE), allows visualization of tissue enhancement while suppressing blood signal. One critical part of FIDDLE is the prep pulse prior to inversion, which accentuates differences in magnetization between tissue and blood. In this study, we compared a T2-prep and a magnetization transfer (MT) prep for use with FIDDLE.

A fat suppressed adiabatic T2-preparation module for 3T

A recently developed T2-preparation module for cardiac imaging at high field is insensitive to B0 and B1 inhomogeneity, cardiac motion and flow. Obtained T2 weighted images exhibit bright fat signal that can obscure the signal of myocardium and other muscles. Therefore, a chemical selective saturation (CHESS) is usually applied for fat suppression after the T2-preparation, e.g. in coronary artery MRI. Its quality is often poor and it is unsuited for longer readout durations. In this study, we propose a new fat suppressed T2-preparation module for 3T using binomial composite RF pulses as 90° pulses to more efficiently suppress fat, maintaining robustness towards inhomogeneity, cardiac motion, and flow. Methods An oil and water phantom was scanned on a Siemens MAGNETOM Trio 3T MR scanner (16-channel coil) to compare the proposed fat-suppression method with the existing T2-preparation using CHESS fat-suppression. The proposed T2-preparation method as shown figure 1 with integrated fat-suppression uses refocusing pulses shown in a previous study [1] to be insensitive to cardiac motion, blood flow, B0 and B1 field. The preparation module is composed of 3 parts. First, a composite binomial pulse consisting of 3 rectangular pulses with1:2:1 amplitude ratio for tipping water spins onto the transverse plane using 22.5° - 45° - 22.5° flip angles. Second, four BIREF-1 [2] pulses for refocusing water spins. Third, a composite binomial pulse (22.5° - 45° - -157.5°) to rotate water and fat spins onto the +Z and -Z axis, respectively. Fat suppression was achieved when the inverted fat spins reached the zero crossing of the fat recovery curve while acquiring the center of k-space during segmented scanning. The scan parameters were ECG gated 2D FLASH sequence, TR/TE = 4.04/1.63 ms, T2-prep time = 40 ms, # of segments = 21, water-fat out of phase time = 1.23 ms, flip angle = 20, FOV = 250 x 210, Matrix = 256 x 216, Thickness = 5 mm, simulation RR = 800 ms, trigger pulse =2 , trigger time =5 80 ms. To evaluate the fat suppression capability of the proposed method, signal-to-noise ratio (SNR), water-fat signal ratio and fat heterogeneity were measured. The heterogeneity was defined as standard deviation of normalized fat signal intensity. Results

Suppression of ghost artifacts arising from long T1 species in segmented inversion‐recovery imaging

We demonstrate an improved segmented inversion‐recovery sequence that suppresses ghost artifacts arising from tissues with long T1 ( > 1.5 s).

Fully Automatic Rapid inversion time (TI) Adjustment for Late Gadolinium Enhancement (LGE) Imaging Using a Pencil Beam Excitation Pulse for Single-Line T1 (SLT1) Mapping of Myocardium

Background LGE requires appropriate TI setting to null viable myocardium, which can be challenging and time consuming. Phase sensitive inversion recovery (PSIR) makes the TI choice less crucial for 2D imaging. However, for 3D PSIR navigator gating is required for both IR and reference data significantly increasing scan time. Additionally using a fixed single TI for a 3D scan while contrast washes out is subpotimal and worsens contrast-to-noise ratio (CNR). If repeated T1 assessment was possible during 3D LGE, scan time could be reduced and CNR optimized. Although TI scout and T1 mapping sequences could be used to determine correct TI, they cannot be executed rapidly and repeatedly during 3D LGE. We developed a rapid SLT1 technique that can be executed repeatedly during 3D or before 2D scans with minimal time loss. It calculates and writes the TI setting into the protocol automatically.

Accuracy of ECV imaging for the detection of subendocardial infarction - comparison with black blood delayed enhancement and pathology

Background Delineation of diseased and normal tissue is fundamental to identifying cardiac pathology. Studies suggest that parametric extracellular volume fraction (ECV) imaging is superior to conventional delayed enhancement for detection of diffuse, global myocardial disease. Conversely, the sensitivity of ECV for the detection of focal disorders is unclear. This may be important for subendocardial disease since the standard methodology for ECV requires that “regions of interest.. have adequate margins of separation from tissue interfaces prone to partial volume averaging such as between myocardium and blood” [1]. We have developed a new, Flow-Independent Dark-blood DeLayed Enhancement technique (FIDDLE) that increases the conspicuity of subendocardial hyperenhancement, by making the blood pool black [2]. In this study, we compared ECV and FIDDLE for the detection of subendocardial infarction as verified by pathology.