Look-Locker Sequence Research Articles

Myocardial scar identification based on analysis of Look–Locker and 3D late gadolinium enhanced MRI

The aim of this study is to introduce and evaluate an approach for objective and reproducible scar identification from late gadolinium enhanced (LGE) MR by analysis of LGE data with post-contrast T(1) mapping from a routinely acquired T(1) scout Look-Locker (LL) sequence. In 90 post-infarction patients, a LL sequence was acquired prior to a three-dimensional LGE sequence covering the entire left ventricle. In 60/90 patients (training set), the T(1) relaxation rates of remote myocardium and dense myocardial scar were linearly regressed to that of blood. The learned linear relationship was applied to 30/90 patients (validation set) to identify the remote myocardium and dense scar, and to normalize the LGE signal intensity to a range from 0 to 100 %. A 50 % threshold was applied to identify myocardial scar. In the validation set, two observers independently performed manual scar identification, annotated reference regions for the full-width-half-maxima (FWHM) and standard deviation (SD) method, and analyzed the LL sequence for the proposed method. Compared with the manual, FWHM, and SD methods, the proposed method demonstrated the highest inter-class correlation coefficient (0.997) and Dice overlap index (98.7 ± 1.3 %) between the two observers. The proposed method also showed excellent agreement with the gold-standard manual scar identification, with a Dice index of 89.8 ± 7.5 and 90.2 ± 6.6 % for the two observers, respectively. Combined analysis of LL and LGE sequences leads to objective and reproducible myocardial scar identification in post-infarction patients.

Cardiac T 1 Imaging

T(1) mapping of the heart has evolved into a valuable tool to evaluate myocardial tissue properties, with or without contrast injection, including assessment of myocardial edema and free water content, extracellular volume (expansion), and most recently cardiomyocyte hypertrophy. The magnetic resonance imaging pulse sequence techniques developed for these applications have had to address at least 2 important considerations for cardiac applications: measure magnetization-inversion recoveries during cardiac motion with sufficient temporal resolution for the shortest expected T(1) values, and, second, obtain these measurements within a time during which a patient can comfortably suspend breathing. So-called Look-Locker techniques, and variants thereof, which all sample multiple points of a magnetization recovery after each magnetization preparation, have therefore become a mainstay in this field. The rapid pace of advances and new findings based on cardiac T(1) mapping for assessment of diffuse fibrosis or myocardial edema show that these techniques enrich the capabilities of magnetic resonance imaging for myocardial tissue profiling, which is arguably unmatched by other cardiac imaging modalities.

Cardiac magnetic resonance T1 mapping pre and post contrast in heart transplant patients with clinical antibody-mediated rejection: a preliminary experience

Background Antibody-mediated rejection (AMR) is characterized by histopathological and immunophenotypic findings such as activated endothelial cells, intravascular macrophages and evidence of capillary C4d deposition. This inflammatory reaction could be followed by diffuse fibrosis. Cardiac magnetic resonance (CMR) with recently T1 mapping is a promising technique to identify diffuse myocardial fibrosis. The purpose of this study was to assess T1 mapping in patients with AMR. Methods Two patients with clinical AMR (histopathological and immunophenotypic findings, presence of donor-specific allo antibodies and allograft dysfunction) performed a CMR study one week (for the first patient) and 3 weeks (for the second patient) after the treatment of AMR (plasmapheresis, IV Immunoglobulins and Rituximab). Images were acquired on a 1.5 Tesla scanner (Siemens) including T1 mapping using a shortened modified look-locker inversion-recovery sequence and T2 mapping in a matched mid-ventricular short axis slice using a black- blood single shot fast spin echo pulse sequence. Segmental and global T1 values were measured before and 15 minutes after administration of 0.2 mmol/kg of Gadoteric acid and compared to our cohort of 17 controls. Results Mean non contrast T1 values were significantly higher in heart transplants patients compared to controls (1100 ± 5 ms vs 947 ± 29 ms, P < 0.001). Segmental T1 values were significantly higher in the 6 regions of interest compared to controls (P < 0.001 in all segments). Mean post contrast T1 values were not significantly different in patients and controls. Mean T2 value was higher in patients compared to controls (73 ± 13 vs 50 ± 4 ms), suggesting the presence of global edema. Conclusions Heart transplant patients with clinical antibodymediated rejection show a significant increased global and segmental non contrast T1 values suggesting the presence of diffuse myocardial fibrosis. Further studies are required to confirm these data. Funding

Extracellular volume assessed by CMR T1-mapping correlates with histologically determined amount of diffuse fibrosis in DCM

Background Diffuse myocardial fibrosis (MF) in dilated cardiomyopathy (DCM) is closely related to systolic and diastolic cardiac failure and could be identified as a major independent value prediciting clinical outcome. It results from elevated levels of collagen and is therefore associated with an expansion of the extracellular volume (ECV). Up to now, the detection of MF requires myocardial biopsy. Recent reports indicate that CMR T1-Mapping has the potential to detect MF non-invasively. We compared the ECV values derived from T1-mapping with the collagen volume fraction (CVF) as meausured in histological samples. Methods All CMR examinations were performed in a 1.5 T CMR scanner (Achieva, Philips Healthcare). Short axis slices covering the left ventricle were acquired using SSFPsequences to measure volumes and ejection fraction. T1- relaxation times were measured from 24 patients (54 ± 13 years,16 males) with DCM before and 15 minutes after injection of gadolinium-DTPA contrast agent (Magnevist, 0.2 mmol/kg body weight). T1-maps were created out of 11 mid-ventricular short axis views with increasing inversion times (TI; 100-4400 msec.) using a single breathhold modified Look-Locker inversion-recovery sequence (MOLLI, TR/TE = 3.5/1.8 msec, flip angle = 35°) in late diastole. The formula for calculating the extracellular volume fractions is given in Figure 1. Myocardial biopsies were taken and stained with Acid Fuchsin Orange-G (AFOG). Tissue collagen content was quantified histologically by using an automated image analysis system and correlated with ECV measurements. Results The DCM patients had a mean left ventricular ejection fraction (LVEF) of 39 ± 16%. Average ECV fraction was 27 ± 4% and CVF was 19 ± 4% in our study population. There was a strong correlation between ECV and CVF (r = 0.85; p = 0.01, Figure 2). Patients with severe

T1 mapping: useful for treatment monitoring in patients with senile systemic amyloidosis?

Background Recent reports indicate that epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, is potent to inhibit fibril formation of several amyloidogenic proteins in vitro. In vivo studies revealed reduction of left ventricular myocardial mass (LVM) after 12 months of daily consumption of 450 mg EGCG. However, the underlying process of LVM reduction, either due to reduction of amyloid or due to atrophy of cardiomyocytes, remained unknown. T1-mapping has the potential to monitor the extent of the extracellular volume (ECV). We sought to investigate the use of T1 mapping for monitoring of treatment effects in a cohort of patients with senile systemic amyloidosis (SSA) treated with EGCG for 12 months. Methods CMR examinations were performed in 8 patients (70 ± 8 years, 7 males) with histologically proven SSA before and 12 months after daily consumption of 450 mg EGCG using a 1.5 T CMR scanner (Achieva, Philips Healthcare). Short axis slices were acquired using SSFPsequences to measure left ventricular volumes, ejection fraction (EF) and LVM. T1-maps were created out of 11 mid-ventricular short axis views with increasing inversion times (TI; 100-4400 msec) using a single breathhold modified Look-Locker inversion-recovery sequence (MOLLI, TR/TE = 3,5/1,8 msec, flip angle = 35°) in late diastole before and 15 minutes after injection of gadolinium-DTPA contrast agent (0.2 mmol/kg body weight). ECV was calculated using the formula given in Figure 1. Results After 12 months of EGCG consumption a significant decrease of LVM (-14.5 ± 12.9 g, p < 0.05, Figure 2) was observed. Moreover, a significant decrease of native T1 (-63.3 ± 64.1 ms, p < 0.05, Figure 2) was noticed. There was no significant change in ECV and EF. Conclusions

T1 values in discrimination between health and disease using different T1 sequences: comparison between 3'3'5-MOLLI, 3'5-MOLLI, shMOLLI and SASHA

Background Myocardial T1 mapping is emerging as a promising means to non-invasively discriminate between normal and diseased myocardium. Original modified Look-Locker sequence (3’3’5-MOLLI) can induce a long breath-hold and is prone to cardiac and respiratory motion. Several shorter sequences (3’5MOLLI, shMOLLI and SASHA) have been proposed for acquisition of T1 values. We examined native and postcontrast T1 values derived by above sequences within the same subject and investigated their ability to separate between health and disease. We further examined reproducibility of measurements within and between observers.

Advanced diffuse fibrosis is associated with mid-wall fibrosis in patients with aortic stenosis

Purpose: To determine the association between diffuse fibrosis by T1 mapping and mid-wall fibrosis (MwF) by delayed enhancement in patients with aortic stenosis (AS). Methods: In a prospective study, patients with AS and no myocardial infarction underwent cardiovascular magnetic resonance (CMR) at 3T. Using modified look-locker inversion sequences, T1 maps were generated pre- and 20 min post-contrast (gadobutrol, 0.1 mmol/kg). Contrast volume of distribution (Vd; ΔRmyocardium/ΔRbloodx[1-hematocrit], where ΔR=1/post-contrast T1–1/pre-contrast T1) was measured at the short-axis, mid-cavity level in patients without MwF. In patients with MwF, Vd was measured at the short-axis level of MwF, excluding regions of enhancement. AS severity was assessed with echocardiography [aortic valve area, mean pressure gradient, trans-aortic velocity (Vm)]. Indices of left ventricular hypertrophy were evaluated with CMR [indexed left ventricular mass (LVMi) and mass/volume ratio (M/V; LVM/end-diastolic volume)]. Logistic regression was used to determine the association between Vd and MwF, adjusting for potential confounders. Results: Sixty patients were studied (70% males; 71±9 years, Vm 3.6±0.9m/s). MwF was identified in 33%. Patients with MwF had higher LVMi (91±22 vs. 79±16g/m2, p=0.03), M/V (1.21±0.22 vs. 1.08±0.19, p=0.02), Vm (3.9±0.7 vs. 3.5±0.9m/s, p=0.04) and Vd (28.7±2.5 vs. 26.7±2.0%, p<0.01). After adjusting for age, gender, AS severity and left ventricular remodeling indices, Vd was independently associated with MwF (odds ratio 1.55, 95% confidence interval 1.04-2.32). ![Figure][1] Conclusions: MwF is independently associated with an increased level of diffuse fibrosis. Diffuse fibrosis by T1 mapping is an early marker of myocardial response to ventricular hypertrophy. [1]: pending:yes

Myocardial Extracellular Volume Fraction From T1 Measurements in Healthy Volunteers and Mice: Relationship to Aging and Cardiac Dimensions

This study aimed to test the characteristics of the myocardial extracellular volume fraction (ECV) derived from pre- and post-contrast T1 measurements among healthy volunteers. Cardiac magnetic resonance (CMR) T1 measurements of myocardium and blood before and after contrast allow quantification of the ECV, a tissue parameter that has been shown to change in proportion to the connective tissue fraction. Healthy volunteers underwent standard CMR imaging with administration of gadolinium. T1 measurements were performed with a Look-Locker sequence followed by gradient-echo acquisition. We tested the segmental, interslice, inter-, intra-, and test-retest characteristics of the ECV, as well as the association of the ECV with other variables. Juvenile and aged mice underwent a similar protocol, and cardiac sections were harvested for measurement of fibrosis. In healthy volunteers (N= 32, 56% female; age 21 to 72 years), the ECV averaged 0.28 ± 0.03 (range 0.23 to 0.33). The intraclass coefficients for the intraobserver, interobserver, and test-retest absolute agreements of the ECV were 0.94 (95% confidence interval: 0.84 to 0.98), 0.93 (95% confidence interval: 0.80 to 0.98), and 0.95 (95% confidence interval: 0.52 to 0.99), respectively. In volunteers, the ECV was associated with age (r= 0.74, p < 0.001), maximal left atrial volume index (r= 0.67, p < 0.001), and indexed left ventricular mass. There were no differences in the ECV between segments in a slice or between slices. In mice (N= 12), the myocardial ECV ranged from 0.20 to 0.32 and increased with age (0.22 ± 0.02 vs. 0.30 ± 0.02, juvenile vs. aged mice, p < 0.001). In mice, the ECV correlated with the extent of myocardial fibrosis (r= 0.94, p < 0.001). In healthy volunteers, the myocardial ECV ranges from 0.23 to 0.33, has acceptable test characteristics, and is associated with age, left atrial volume, and left ventricular mass. In mice, the ECV also increases with age and strongly correlates with the extent of myocardial fibrosis.

Three-dimensional Look-Locker MRI for evaluation of postcontrast myocardial and blood T1 values: Comparison with two-dimensional Look-Locker and late gadolinium enhancement MRI

Two-dimensional (2D) Look-Locker MRI technique can identify myocardial fibrosis, but cannot cover the whole left ventricle during a single scan. To develop breath-hold three-dimensional (3D) Look-Locker MRI for the evaluation of postcontrast myocardial and blood T1 values and myocardial scarring in the left ventricle. A phantom and 24 patients with myocardial diseases underwent gadolinium-enhanced 2D and 3D Look-Locker MRI using a 1.5-T unit. We compared the T1 value of the phantom and the values of the myocardium and blood in the patients between the two Look-Locker MRI sequences. In the patient study, the scan ordering of the two Look-Locker MRI was selected randomly. We also assessed the ability of the 3D imaging to detect myocardial scarring that was confirmed by late gadolinium enhancement MRI. The phantom study showed a good agreement for the T1 value between 2D and 3D Look-Locker MRI. There were no significant differences in the myocardial T1 values after contrast between 2D and 3D Look-Locker MRI or in the T1 values between the two imaging slices on the 3D Look-Locker MRI (P > 0.10). A better agreement for the myocardial T1 values was found when the 3D Look-Locker imaging was performed first. The T1 values for blood were affected by the scan order (P < 0.05). The 3D Look-Locker MRI showed myocardial scarring with a shorter T1 value (290.4 ± 62.7 ms) than those for unscarred myocardium (360.8 ± 30.3 ms). Three-dimensional Look-Locker MRI may precisely estimate the postcontrast myocardial and blood T1 values for the entire left ventricle during a single scan.

A new method for objective myocardial scar characterization using MR late gadolinium enhancement and post-contrast look-locker sequences

Background Accurate characterization of myocardial scar has important diagnostic and prognostic implications for post-infarct patients. Previous studies have used late gadolinium enhanced (LGE) MR to characterize myocardial scar, by dividing the scar region into core and gray zones based on signal intensity in LGE. The characterization is however subjective to manual annotations, dependent on image acquisition parameters, contrast dose and timing, and has limited reproducibility. The purpose of this study is to objectively and reproducibly characterize infarcted myocardial tissue combining information from the LGE and post-contrast Look-Locker (LL) sequences.

T1 mapping is abnormal before decline in EF in patients with Becker and Duchenne muscular dystrophy

Background Patients with Duchenne muscular dystrophy (DMD) develop cardiomyopathy (CM) at an earlier age compared to Becker muscular dystrophy (BMD), but the age of onset within each diagnosis is variable. A method to predict CM onset associated with dystrophinopathy could alter therapeutic approaches and improve outcomes. Shortened post-contrast T1 relaxation times are an early marker of myocardial fibrosis and are abnormal in patients with DMD as described in our previous work. To our knowledge, T1 mapping has not been evaluated in BMD patients. We hypothesized that patients with BMD would also have abnormal T1 times and that these abnormalities would precede LV dysfunction. Methods Twenty-six CMR scans from these 2 dystrophinopathy populations (N=5 BMD and N=21 DMD) were compared with 10 CMR scans from control patients without cardiovascular disease. T1 maps were created from the Look-Locker sequence, obtained 10 minutes after gadolinium injection, using MRMap. Using MatLab, T1 times were obtained for every voxel in 6 standard myocardial segments in the short axis at the level of the papillary muscles. Mean T1 times were compared between BMD, DMD and controls using a Kruskal Wallis test. A subset of patients with normal LVEF and dystrophinopathy (BMD or DMD) was compared to controls using a Mann-Whitney U test. Results The mean age of patients was 25.4 ± 8.1 years in the BMD group, 15.7 ± 4.3 years in the DMD group, and 16.9 ± 1.3 years in controls. One patient with BMD and 13 patients with DMD had LVEF < 55%. Two patients from both BMD and DMD had LV dilatation. BMD and DMD patients had significantly shorter mean postcontrast T1 compared with controls (BMD: 355 ms, 95% CI (314, 395), DMD:357 ms, 95% CI (323, 390), control: 420 ms, 95% CI (389, 451), p=0.035) (Figure 1). The subset of BMD and DMD patients and normal LVEF also had a significant decrease in post-contrast T1 when compared to controls (-52.4 ms, 95% CI (-7.2, -97.5), p=0.018) (Figure 2). Conclusions Myocardial post-contrast T1 relaxation times in BMD and DMD are significantly shorter than in controls. They remain significantly decreased in the subset of patients with normal LVEF, suggesting that CMR may have prognostic utility in detecting subclinical myocardial damage associated with loss of dystrophin prior to a decline in LVEF. Further longitudinal study is necessary to evaluate whether T1 times can predict future onset of CM in BMD and DMD. Funding none.

Standardization of myocardial T1 time measurements in clinical setting using MOLLI, shMOLLI and LL at 1.5T and 3T - the CONSEPT study

Background MMeasurement of myocardial T1 mapping is possible with most of the clinically used magnets using sequences based on modification (MOLLI) or shortening (shMOLLI) of the Look-Locker (LL) sequence. However, the robustness of T1 post-processing approaches has not been systematically examined for these sequences, nor for different field strengths, in native and post-contrast T1 maps. Moreover, repeatability of measurements in conditions with altered geometric relations of cardiac chambers and wall thickness commonly observed in clinical settings remains unknown.

Comparison of look-locker and MOLLI sequences for T1 mapping in hypertrophic and ischemic cardiomyopathy

Methods 5 control patients (4M/1F, age 44±21 y) with normal left ventricular (LV) function and no history of heart disease, 5 patients with ICM (3M/2F, 63±2 y), and 16 patients with HCM (10M/6F, age 51±15y) were recruited into an IRB approved protocol. All subjects were imaged at 1.5T (Achieva XR, Philips). T1 mapping was performed using MOLLI and LL at 2 LV short axis levels (basaland midcavity) before and after contrast agent injection (Magnevist; 0.2 mmol/kg). Post gadopentetate dimeglumine (Magnevist; 0.2 mmol/kg) injection time was about 15 min for HCM and ICM patients and was shorter (about 5 min) for the controls due to organizational reasons. For each subject, TI measurements were made in 6 ROIs per level.

Estimation of cardiac amyloid infiltration with myocardial T1 mapping correlates with severity of cardiac involvement

Background Post-contrast myocardial T1-mapping with cardiac magnetic resonance (CMR) has shown usefulness in the diagnosis of cardiac amyloid. A lower value indicates increase in extracellular volume and thereby amyloid deposition. The aim of this study is to assess the association between the amount of amyloid deposition as estimated by the degree of post-contrast myocardial T1 reduction and the severity of left ventricular (LV) involvement in cardiac amyloidosis. Methods Consecutive patients referred for 3.0 Tesla CMR with a final diagnosis of cardiac amyloidosis (defined as positive cardiac biopsy and/or typical diffuse, predominantly subendocardial pattern of delayed contrast enhancement) were retrospectively evaluated. The septal E/E’ ratio as an index of LV filling pressures was measured with doppler echocardiography (n=18, 69%). Indexed LV volumes and mass, LV ejection fraction, and LV basal anteroseptal and inferolateral wall thicknesses were determined from cine CMR. Hemodynamic data from cardiac catheterization and brain natriuretic peptide (BNP) serum levels were available in 9 (36%) and 14 (54%) patients. respectively. Myocardial, endocardial, blood, and skeletal muscle were quantified after Gd-DTPA administration on a previously validated Look-Locker sequence using dedicated software. Correlations between myocardial T1 values and other indices of cardiac involvement were performed using Pearson correlation coefficients. Results We included 26 patients (17 males [65.4%], age 68±13 years) with a final diagnosis of cardiac amyloid. There was an inverse correlation between myocardial/blood T1 ratio and basal anteroseptal (r=-0.519, p=0.008) and inferolateral (r=-0.498, p=0.011) wall thickness. Similarly endocardial/blood T1 ratio was inversely correlated with basal anteroseptal (r=-0.595, p=0.002; Figure) and inferolateral (r=-0.429, p=0.032) wall thickness. No significant associations were noted with LV volumes, ejection fraction, or mass. Otherwise, myocardial and endocardial T1 time showed an inverse correlation with BNP (r=-0.659, p=0.014 and r=-0.610, p=0.027 respectiveley). In addition, myocardial/skeletal muscle T1 ratio showed

Are T1 values to characterize myocardial tissue equivalent between various sequences: comparison of MOLLI, shMOLLI, 3'5-MOLLI and SASHA

Background Classical modified Look-Locker sequence (MOLLI) can induce a long breath-hold and is prone to cardiac and respiratory motion. Several shorter sequences based on inversion (3’5MOLLI, shMOLLI) and saturation recovery (SASHA) of longitudinal relaxation have been proposed for derivation of T1 values or calculation of extracellular volume fraction or lambdas. Despite the validation in T1 gel phantoms, it has not been determined whether these novel sequences provide equivalent information on T1 when performed within the same individual. Methods Twenty-three subjects underwent T1 mapping in a midventricular equatorial short axis slice using above sequences on 3T clinical scanner prior and after gadolinium contrast (0.2 mmol/kg) administration. The images were analyzed using PRIDE tool with in-built automated motion correction. ROIs were drawn conservatively within the septal and lateral myocardium and the blood pool. Comparison of the native T1 values and lambdas were performed and expressed as percentage of mean difference from the values obtained with goldstandard MOLLI sequence.

Gadobenate Dimeglumine (Multihance) in Mr Angiography: An In-Vitro Phantom Comparison with Gadopentetate Dimeglumine (Magnevist) at Different Concentrations

Numerous clinical studies suggest that gadobenate dimeglumine is diagnostically superior to other gadolinium chelates for MR imaging applications, including contrast-enhanced MR angiography (CE-MRA). However, confirmatory in-vitro phantom studies have thus far been lacking. To evaluate the difference in signal intensity achieved with the high-relaxivity MR contrast agent gadobenate dimeglumine (MultiHance) relative to that achieved with the standard-relaxivity non-specific agent gadopentetate dimeglumine (Magnevist) at different concentrations using an in-vitro phantom study design. Test tubes with whole human blood were prepared with concentrations of gadobenate dimeglumine or gadopentetate dimeglumine ranging from 0 to 12 mM. A three-dimensional (3D) T1-weighted gradient echo sequence normally used for CE-MRA of the renal arteries was performed at flip angles of 25° and 35°. The signal-to-noise ratio (SNR) was calculated for all concentrations of both contrast agents. Furthermore a Look-Locker sequence was used and quantitative T1 mapping was performed for all the test tubes. The contrast agent concentration in the aorta was simulated using previously published data on T1 in the aorta during the first pass of a contrast agent. The differences between gadobenate dimeglumine and gadopentetate dimeglumine were compared at the simulated concentrations. The SNR achieved with gadobenate dimeglumine was consistently greater than that achieved with gadopentetate dimeglumine at all concentrations. An improvement of 15-25% in SNR was obtained when increasing the flip angle from 25° to 35°. The relative improvement in SNR with gadobenate dimeglumine relative to gadopentetate dimeglumine ranged from 25-72% and was markedly greater at lower concentrations with a flip angle of 35°. Our findings suggest that the relative benefit of gadobenate dimeglumine over gadopentetate dimeglumine for CE-MRA applications is greater at lower concentrations.

T1 Mapping in Cardiomyopathy at Cardiac MR: Comparison with Endomyocardial Biopsy

To determine the utility of cardiac magnetic resonance (MR) T1 mapping for quantification of diffuse myocardial fibrosis compared with the standard of endomyocardial biopsy. This HIPAA-compliant study was approved by the institutional review board. Cardiomyopathy patients were retrospectively identified who had undergone endomyocardial biopsy and cardiac MR at one institution during a 5-year period. Forty-seven patients (53% male; mean age, 46.8 years) had undergone diagnostic cardiac MR and endomyocardial biopsy. Thirteen healthy volunteers (54% male; mean age, 38.1 years) underwent cardiac MR as a reference. Myocardial T1 mapping was performed 10.7 minutes ± 2.7 (standard deviation) after bolus injection of 0.2 mmol/kg gadolinium chelate by using an inversion-recovery Look-Locker sequence on a 1.5-T MR imager. Late gadolinium enhancement was assessed by using gradient-echo inversion-recovery sequences. Cardiac MR results were the consensus of two radiologists who were blinded to histopathologic findings. Endomyocardial biopsy fibrosis was quantitatively measured by using automated image analysis software with digital images of specimens stained with Masson trichrome. Histopathologic findings were reported by two pathologists blinded to cardiac MR findings. Statistical analyses included Mann-Whitney U test, analysis of variance, and linear regression. Median myocardial fibrosis was 8.5% (interquartile range, 5.7-14.4). T1 times were greater in control subjects than in patients without and in patients with evident late gadolinium enhancement (466 msec ± 14, 406 msec ± 59, and 303 msec ± 53, respectively; P < .001). T1 time and histologic fibrosis were inversely correlated (r = -0.57; 95% confidence interval: -0.74, -0.34; P < .0001). The area under the curve for myocardial T1 time to detect fibrosis of greater than 5% was 0.84 at a cutoff of 383 msec. Cardiac MR with T1 mapping can provide noninvasive evidence of diffuse myocardial fibrosis in patients referred for evaluation of cardiomyopathy.

TU‐G‐217A‐05: Improved Look‐Locker Acquisition Scheme and Curve Fitting Procedure

Purpose: To improve the quality of 3D Look‐Locker (LL) T1 mapping by optimizing the k‐space segmentation in MRI. In addition, a multi‐step curve fitting procedure is developed to reduce the effect of curve fitting error on the T1 estimation. Methods: Traditional 3D LL acquisition generally utilizes centric encoding scheme that is limited to single phase encoding direction. To minimize reconstruction artifacts, we optimized the k‐space segmentation by implementing the elliptical segmentation scheme along both phase encoding directions. We also developed a multi‐step curve fitting procedure to compute the T1 values. First, four‐parameter curve fit (flip angle, inversion angle, equilibrium magnetization and T1) is performed to obtain the angle maps. Then, the acquired angle maps are smoothed based on the chi‐square weighting of the fit. These smoothed angle maps are treated as the actual angle maps and a two‐parameter (equilibrium magnetization and T1) fit is used to create the final T1 map. Simulation and phantom study were performed to assess the performance of the proposed LL modification and the multi‐step fitting algorithm. Results: Reconstruction artifacts are reduced using the elliptical segmentation scheme relative to the traditional encoding method. In addition, the subsequent T1 computation using the elliptical encoding data along with the chi‐square weighted angle maps is shown to yield more precise T1 values and was more immune to fitting errors. Conclusions: An elliptical centric k‐ space segmentation scheme is implemented on a 3D LL sequence to reduce reconstruction artifacts. A multi‐step curve fitting procedure that uses chi‐ square weighting is used to reduce the effect of false angles obtained from spurious signal. These methods were shown to improve the precision and accuracy of 3D LL T1 estimation.

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Cardiac arterial spin labeling using segmented ECG‐gated Look‐Locker FAIR: Variability and repeatability in preclinical studies

MRI is important for the assessment of cardiac structure and function in preclinical studies of cardiac disease. Arterial spin labeling techniques can be used to measure perfusion noninvasively. In this study, an electrocardiogram-gated Look-Locker sequence with segmented k-space acquisition has been implemented to acquire single slice arterial spin labeling data sets in 15 min in the mouse heart. A data logger was introduced to improve data quality by: (1) allowing automated rejection of respiration-corrupted images, (2) providing additional prospective gating to improve consistency of acquisition timing, and (3) allowing the recombination of uncorrupted k-space lines from consecutive data sets to reduce respiration corruption. Finally, variability and repeatability of perfusion estimation within-session, between-session, between-animal, and between image rejection criteria were assessed in mice. The criterion used to reject images from the T(1) fit was shown to affect the perfusion estimation. These data showed that the between-animal coefficient of variability (24%) was greater than the between-session variability (17%) and within-session variability (11%). Furthermore, the magnitude of change in perfusion required to detect differences was 30% (within-session) and 55% (between-session) according to Bland-Altman repeatability analysis. These technique developments and repeatability statistics will provide a platform for future preclinical studies applying cardiac arterial spin labeling.