Simultaneous Acquisition of Diffusion Tensor and Dynamic Diffusion MRI.

BACKGROUND: Dynamic diffusion magnetic resonance imaging (ddMRI) metrics can assess transient microstructural alterations in tissue diffusivity but requires additional scan time hindering its clinical application. PURPOSE: To determine whether a diffusion gradient table can simultaneously acquire data to estimate dynamic and diffusion tensor imaging (DTI) metrics. STUDY TYPE: Prospective. SUBJECTS: Seven healthy subjects, 39 epilepsy patients (15 female, 31 male, age ± 15). FIELD STRENGTH/SEQUENCE: Two-dimensional diffusion MRI (b = 1000 s/mm2 ) at a field strength of 3 T. Sessions in healthy subjects-standard ddMRI (30 directions), standard DTI (15 and 30 directions), and nested cubes scans (15 and 30 directions). Sessions in epilepsy patients-two 30 direction (standard ddMRI, 10 nested cubes) or two 15 direction scans (standard DTI, 5 nested cubes). ASSESSMENT: Fifteen direction DTI was repeated twice for within-session test-retest measurements in healthy subjects. Bland-Altman analysis computed bias and limits of agreement for DTI metrics using test-retest scans and standard 15 direction vs. 5 nested cubes scans. Intraclass correlation (ICC) analysis compared tensor metrics between 15 direction DTI scans (standard vs. 5 nested cubes) and the coefficients of variation (CoV) of trace and apparent diffusion coefficient (ADC) between 30 direction ddMRI scans (standard vs. 10 nested cubes). STATISTICAL TESTS: Bland-Altman and ICC analysis using a P-value of 0.05 for statistical significance. RESULTS: Correlations of mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were strong and significant in gray (ICC > 0.95) and white matter (ICC > 0.95) between standard vs. nested cubes DTI acquisitions. Correlation of white matter fractional anisotropy was also strong (ICC > 0.95) and significant. ICCs of the CoV of dynamic ADC measured using repeated cubes and nested cubes acquisitions were modest (ICC >0.60), but significant in gray matter. CONCLUSION: A nested cubes diffusion gradient table produces tensor-based and dynamic diffusion measurements in a single acquisition. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Nonalcoholic Fatty Liver Disease in Patients with Inherited and Sporadic Motor Neuron Degeneration.

We describe evidence of fatty liver disease in patients with forms of motor neuron degeneration with both genetic and sporadic etiology compared to controls. A group of 13 patients with motor neuron disease underwent liver imaging and laboratory analysis. The cohort included five patients with hereditary spastic paraplegia, four with sporadic amyotrophic lateral sclerosis (ALS), three with familial ALS, and one with primary lateral sclerosis. A genetic mutation was reported in nine of the thirteen motor neuron disease (MND) patients. Fatty liver disease was detected in 10 of 13 (77%) MND patients via magnetic resonance spectroscopy, with an average dome intrahepatic triacylglycerol content of 17% (range 2-63%, reference ≤5.5%). Liver ultrasound demonstrated evidence of fatty liver disease in 6 of the 13 (46%) patients, and serum liver function testing revealed significantly elevated alanine aminotransferase levels in MND patients compared to age-matched controls. Fatty liver disease may represent a non-neuronal clinical component of various forms of MND.

Left Ventricular Structure, Tissue Composition, and Aortic Distensibility in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications.

Alterations in myocardial structure, function, tissue composition (e.g., fibrosis) may be associated with metabolic syndrome (MetS). This study aimed to determine the relation of MetS and its individual components to markers of cardiovascular disease in patients with type 1 Diabetes Mellitus (T1DM). A total of 978 subjects of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications T1DM cohort (age: 49 ± 7 years, 47% female, DM duration 28 ± 5 years) underwent cardiovascular magnetic resonance. In a subset of 200 patients, myocardial tissue composition was measured with cardiovascular magnetic resonance T1 mapping after contrast administration. MetS was defined as T1DM plus 2 other abnormalities based on the American Heart Association/National Cholesterol Education Program criteria. MetS was present in 34.1% of subjects. After adjustment for age, height, scanner, study cohort, gender, smoking, mean glycated hemoglobin levels, history of macroalbuminuria and end-stage renal disease, left ventricle mass was greater by 12.3 g, end-diastolic volume was higher by 5.4 ml, and mass to end-diastolic volume ratio was higher by 5% in patients with MetS versus those without MetS (p <0.001 for all). Myocardial T1 times were lower by 29 ms in patients with MetS than those without (p <0.001). Elevated waist circumference showed the strongest associations with left ventricle mass (+10.1 g), end-diastolic volume (+6.7 ml), and lower myocardial T1 times (+31 ms) in patients with MetS compared with those without (p <0.01). In conclusion, in a large cohort of patients with T1DM, 34.1% of subjects met MetS criteria. MetS was associated with adverse myocardial structural remodeling and change in myocardial tissue composition.

Highly Efficient and Accurate Deep Learning-Based Classification of MRI Contrast on a CPU and GPU.

Classifying MR images based on their contrast mechanism can be useful in image segmentation where additional information from different contrast mechanisms can improve intensity-based segmentation and help separate the class distributions. In addition, automated processing of image type can be beneficial in archive management, image retrieval, and staff training. Different clinics and scanners have their own image labeling scheme, resulting in ambiguity when sorting images. Manual sorting of thousands of images would be a laborious task and prone to error. In this work, we used the power of transfer learning to modify pretrained residual convolution neural networks to classify MRI images based on their contrast mechanisms. Training and validation were performed on a total of 5169 images belonging to 10 different classes and from different MRI vendors and field strengths. Time for training and validation was 36 min. Testing was performed on a different data set with 2474 images. Percentage of correctly classified images (accuracy) was 99.76%. (A deeper version of the residual network was trained for 103 min and showed slightly lower accuracy of 99.68%.) In consideration of model deployment in the real world, performance on a single CPU computer was compared with GPU implementation. Highly accurate classification, training, and testing can be achieved without use of a GPU in a relatively short training time, through proper choice of a convolutional neural network and hyperparameters, making it feasible to improve accuracy by repeated training with cumulative training sets. Techniques to improve accuracy further are discussed and demonstrated. Derived heatmaps indicate areas of image used in decision making and correspond well with expert human perception. The methods used can be easily extended to other classification tasks with minimal changes.

Nonhuman primates exposed to Zika virus in utero are not protected against reinfection at 1 year postpartum.

There is limited information about the impact of Zika virus (ZIKV) exposure in utero on the anti-ZIKV immune responses of offspring. We infected six rhesus macaque dams with ZIKV early or late in pregnancy and studied four of their offspring over the course of a year postpartum. Despite evidence of ZIKV exposure in utero, we observed no structural brain abnormalities in the offspring. We detected infant-derived ZIKV-specific immunoglobulin A antibody responses and T cell memory responses during the first year postpartum in the two offspring born to dams infected with ZIKV early in pregnancy. Critically, although the infants had acquired some immunological memory of ZIKV, it was not sufficient to protect them against reinfection with ZIKV at 1 year postpartum. The four offspring reexposed to ZIKV at 1 year postpartum all survived but exhibited acute viremia and viral tropism to lymphoid tissues; three of four reexposed offspring exhibited spinal cord pathology. These data suggest that macaque infants born to dams infected with ZIKV during pregnancy remain susceptible to postnatal infection and consequent neuropathology.

Inversion Recovery Susceptibility Weighted Imaging With Enhanced T2 Weighting at 3 T Improves Visualization of Subpial Cortical Multiple Sclerosis Lesions.

OBJECTIVES: Cortical demyelination is common in multiple sclerosis (MS) and can be extensive. Cortical lesions contribute to disability independently from white matter lesions and may form via a distinct mechanism. However, current magnetic resonance imaging methods at 3 T are insensitive to cortical, and especially subpial cortical, lesions. Subpial lesions are well seen on T2*-weighted imaging at 7 T, but T2*-weighted methods on 3 T scanners are limited by poor lesion-to-cortex and cerebrospinal fluid-to-lesion contrast. We aimed to develop and evaluate a cerebrospinal fluid-suppressed, T2*-weighted sequence optimized for subpial cortical lesion visualization. MATERIALS AND METHODS: We developed a new magnetic resonance imaging sequence, inversion recovery susceptibility weighted imaging with enhanced T2 weighting (IR-SWIET; 0.8 mm × 0.8 mm in plane, 0.64 mm slice thickness with whole brain coverage, acquisition time ~5 minutes). We compared cortical lesion visualization independently on IR-SWIET (median signal from 4 acquisitions), magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE), double inversion recovery (DIR), T2*-weighted segmented echo-planar imaging, and phase-sensitive inversion recovery images for 10 adults with MS. We also identified cortical lesions with a multicontrast reading of IR-SWIET (median of 2 acquisitions), MP2RAGE, and fluid-attenuated inversion recovery (FLAIR) images for each case. Lesions identified on 3 T images were verified on "gold standard" 7 T T2* and MP2RAGE images. RESULTS: Cortical, and particularly subpial, lesions appeared much more conspicuous on IR-SWIET compared with other 3 T methods. A total of 101 true-positive subpial lesions were identified on IR-SWIET (average per-participant sensitivity vs 7 T, 29% ± 8%) versus 36 on MP2RAGE (5% ± 2%; comparison to IR-SWIET sensitivity, P = 0.07), 17 on FLAIR (2% ± 1%; P < 0.05), 28 on DIR (6% ± 2%; P < 0.05), 42 on T2*-weighted segmented echo-planar imaging (11% ± 5%; P < 0.05), and 13 on phase-sensitive inversion recovery (4% ± 2%; P < 0.05). When a combination of IR-SWIET, MP2RAGE, and FLAIR images was used, a total of 147 subpial lesions (30% ± 5%) were identified versus 83 (16% ± 3%, P < 0.01) on a combination of DIR, MP2RAGE, and FLAIR. More cases had at least 1 subpial lesion on IR-SWIET, and IR-SWIET improved cortical lesion subtyping accuracy and correlation with 7 T subpial lesion number. CONCLUSIONS: Subpial lesions are better visualized on IR-SWIET compared with other 3 T methods. A 3 T protocol combining IR-SWIET with MP2RAGE, in which leukocortical lesions are well seen, improves cortical lesion visualization over existing approaches. Therefore, IR-SWIET may enable improved MS diagnostic specificity and a better understanding of the clinical implications of cortical demyelination.

Determining the optimal postlabeling delay for arterial spin labeling using subject-specific estimates of blood velocity in the carotid artery.

BACKGROUND: Arterial spin labeling with 3D acquisition requires determining a single postlabeling delay (PLD) value. PLD affects the signal-to-noise ratio (SNR) per unit time as well as quantitative cerebral blood flow (CBF) values due to its bearing on the presence of a vascular signal. PURPOSE: To search for an optimal PLD for pseudocontinuous arterial spin labeling (pCASL) using patient-specific carotid artery blood velocity measurements. STUDY TYPE: Prospective. SUBJECTS: A control group of 11 volunteers with no known pathology. Corroboration was through a separate group of six volunteers and a noncontrol group of five sickle cell disease (SCD) patients. FIELD STRENGTH/SEQUENCE: Pseudocontinuous arterial spin labeling with 3D nonsegmented echo planar imaging acquisition at 3T. ASSESSMENT: A perfusion-based measure was determined over a range of PLDs for each of 11 volunteers. A third-order polynomial was used to find the optimal PLD where the defined measure was maximum. This was plotted against the corresponding carotid artery velocity to determine a relationship between the perfusion measure and velocity. Corroboration was done using a group of six volunteers and a noncontrol group of five patients with SCD. PLD was determined from the carotid artery velocity and derived relationship and compared with optimal PLD obtained from measured perfusion over a range of PLD values. Error between the perfusion measure at predicted and measured optimal PLD was determined. STATISTICAL TESTS: Chi-squared goodness of fit; Pearson correlation; Bland-Altman. RESULTS: Carotid artery velocity was 63.8 ± 6.6 cm/s (53.1 ≤ v ≤ 72.3 cm/s) while optimal PLD was 1374 ± 226.5 msec (1102 ≤ PLD ≤ 1787 msec) across the 11 volunteers. PLD as a function of carotid velocity was determined to be PLD = -31.94. v + 3410 msec (Pearson correlation -0.93). In six volunteers, mean error between the perfusion measure at predicted and measured optimal PLD was 1.35%. Pearson correlation between the perfusion measure at the predicted PLD and the measure obtained experimentally was r = 0.96 (P < 0.001). Bland-Altman revealed a slight bias of 1.3%. For the test case of five SCD patients, the mean error was 1.3%. DATA CONCLUSION: Carotid artery velocity was used to determine optimal PLD for pCASL with 3D acquisition. The derived relationship was used to predict optimal PLD and the associated perfusion measure, which was found to be accurate when compared with its measured counterpart. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:951-960.

Myocardial T1 mapping and determination of partition coefficients at 3 tesla: comparison between gadobenate dimeglumine and gadofosveset trisodium.

OBJECTIVE: To compare an albumin-bound gadolinium chelate (gadofosveset trisodium) and an extracellular contrast agent (gadobenate dimeglumine), in terms of their effects on myocardial longitudinal (T1) relaxation time and partition coefficient. MATERIALS AND METHODS: Study subjects underwent two imaging sessions for T1 mapping at 3 tesla with a modified look-locker inversion recovery (MOLLI) pulse sequence to obtain one pre-contrast T1 map and two post-contrast T1 maps (mean 15 and 21 min, respectively). The partition coefficient was calculated as ΔR1myocardium /ΔR1blood , where R1 is 1/T1. RESULTS: A total of 252 myocardial and blood pool T1 values were obtained in 21 healthy subjects. After gadolinium administration, the myocardial T1 was longer for gadofosveset than for gadobenate, the mean difference between the two contrast agents being -7.6 ± 60 ms (p = 0.41). The inverse was true for the blood pool T1, which was longer for gadobenate than for gadofosveset, the mean difference being 56.5 ± 67 ms (p < 0.001). The partition coefficient (λ) was higher for gadobenate than gadofosveset (0.41 vs. 0.33), indicating slower blood pool washout for gadofosveset than for gadobenate. CONCLUSION: Myocardial T1 times did not differ significantly between gadobenate and gadofosveset. At typical clinical doses of the contrast agents, partition coefficients were significantly lower for the intravascular contrast agent than for the extravascular agent.

Myocardial T1 mapping and determination of partition coefficients at 3 tesla: comparison between gadobenate dimeglumine and gadofosveset trisodium / Mapa T1 e coeficiente de partição do miocárdio em aparelho 3 tesla: comparação entre gadobenato de dimeglumina e gadofosveset trissódico

Abstract Objective: To compare an albumin-bound gadolinium chelate (gadofosveset trisodium) and an extracellular contrast agent (gadobenate dimeglumine), in terms of their effects on myocardial longitudinal (T1) relaxation time and partition coefficient. Materials and Methods: Study subjects underwent two imaging sessions for T1 mapping at 3 tesla with a modified look-locker inversion recovery (MOLLI) pulse sequence to obtain one pre-contrast T1 map and two post-contrast T1 maps (mean 15 and 21 min, respectively). The partition coefficient was calculated as ΔR1myocardium /ΔR1blood , where R1 is 1/T1. Results: A total of 252 myocardial and blood pool T1 values were obtained in 21 healthy subjects. After gadolinium administration, the myocardial T1 was longer for gadofosveset than for gadobenate, the mean difference between the two contrast agents being −7.6 ± 60 ms (p = 0.41). The inverse was true for the blood pool T1, which was longer for gadobenate than for gadofosveset, the mean difference being 56.5 ± 67 ms (p < 0.001). The partition coefficient (λ) was higher for gadobenate than gadofosveset (0.41 vs. 0.33), indicating slower blood pool washout for gadofosveset than for gadobenate. Conclusion: Myocardial T1 times did not differ significantly between gadobenate and gadofosveset. At typical clinical doses of the contrast agents, partition coefficients were significantly lower for the intravascular contrast agent than for the extravascular agent.

Resumo Objetivo: Avaliar o efeito da utilização de um agente de contraste intravascular baseado em gadolínio quelado a albumina (gadofosveset) no tempo T1 e no coeficiente de partição do miocárdio, quando comparado com um agente de contraste extravascular baseado no gadolínio não quelado a albumina (gadobenato). Materiais e Métodos: Os participantes do estudo foram submetidos a dois exames para aquisições do mapeamento T1 em aparelho de 3 tesla. Utilizando uma sequência de pulso modificada - modified look-locker inversion recovery (MOLLI) -, realizou-se uma etapa pré-contraste e duas etapas pós-contraste do mapa T1 (média de 15 e 21 minutos). O coeficiente de partição foi calculado como: ΔR1miocárdio /ΔR1sangue. Resultados: Um total de 252 valores de mapa T1 no miocárdio e no sangue foi obtido em 21 indivíduos saudáveis. Após a administração do meio de contraste, a diferença média do tempo T1 do miocárdio entre os agentes de contraste foi -7,6 ± 60 ms (p = 0,41) (isto é, gadobenato T1 < gadofosveset T1). Já no sangue, a diferença média de tempo T1 foi 56,5 ± 67 ms (p < 0,001) (isto é, gadobenato T1 > gadofosveset T1). O coeficiente de partição foi maior para o gadobenato (λ = 0,41) do que para o gadofosveset (λ = 0,33), refletindo uma eliminação mais lenta do gadofosveset em comparação com o gadobenato. Conclusão: Os tempos T1 do miocárdio não foram significativamente diferentes entre gadobenato e gadofosveset. Os coeficientes de partição foram significativamente mais baixos para o agente de contraste intravascular em comparação com o agente extravascular em doses clínicas típicas de cada contraste.

Correlation between right ventricular T1 mapping and right ventricular dysfunction in non-ischemic cardiomyopathy.

Right ventricular (RV) fibrosis is increasingly recognized as the underlying pathological substrate in a variety of clinical conditions. We sought to employ cardiac magnetic resonance (CMR) techniques of strain imaging and longitudinal relaxation time (T1) mapping to better examine the relationship between RV function and structure. Our aim was to initially evaluate the feasibility of these techniques to evaluate the right ventricle. We then sought to explore the relationship between RV function and underlying fibrosis, along with examining the evolution of RV remodeling according to the amount of baseline fibrosis. Echocardiography was performed in 102 subjects with non-ischemic cardiomyopathy. Right ventricular parameters were assessed including: fractional area change (FAC) and longitudinal strain. The same cohort underwent CMR. Post-contrast T1 mapping was performed as a marker of fibrosis with a Look-Locker technique using inversion recovery imaging. Mid-ventricular post-contrast T1 values of the RV free wall, RV septum and lateral LV were calculated using prototype analysis software. Biventricular volumetric data including ejection fraction was measured by CMR using a cine short axis stack. CMR strain analysis was also performed to assess 2D RV longitudinal and radial strain. Simultaneous biochemical and anthropometric data were recorded. Subjects were followed over a median time of 29 months (IQR 20-37 months) with echocardiography to evaluate temporal change in RV FAC according to baseline post-contrast T1 values. Longitudinal data analysis was performed to adjust for patient loss during follow-up. Subjects (62% men, 51 ± 15 years) had mild to moderately impaired global RV systolic function (RVEF = 39 ± 15%; RVEDV = 187 ± 69 ml; RVESV = 119 ± 68 ml) and moderate left ventricular dysfunction at baseline (LVEF 30 ± 17%). Good correlation was observed between mean LV and RV post-contrast T1 values (r = 0.652, p < 0.001), with similar post-contrast T1 values maintained in both the RV free wall and septum (r = 0.761, p < 0.001). CMR RVEF demonstrated a proportional correlation with echocardiographic measures of RV longitudinal function and CMR RV strain (longitudinal r = -0.449, p = 0.001; radial r = -0.549, p < 0.001). RVEF was related to RV post-contrast T1 values, particularly in those with RV dysfunction (free wall T1 r = 0.259 p = 0.027; septal T1 r = 0.421 p < 0.001). RV strain was also related to RV post-contrast T1 values (r = -0.417, p = 0.002). Linear regression analysis demonstrated strain and post-contrast T1 values to be independently associated with RVEF. Subjects with severe RV dysfunction (CMR RVEF <25%) demonstrated lower RV CMR strain (longitudinal p = 0.018; radial p < 0.001), RV T1 values (free wall p = 0.013; septum <0.001) and RV longitudinal echocardiography parameters despite no difference in afterload. During follow-up, those with RV free wall post-contrast T1 values ≥ 350 ms demonstrated ongoing improvement in FAC (Δ6%), whilst values <350 ms were associated with deterioration in RV function (ΔFAC = -5%) (p = 0.026). CMR provides a comprehensive method by which to evaluate right ventricular function. Post-contrast T1 mapping and CMR strain imaging are technically feasible and provide incremental information regarding global RV function and structure. The proportional relationship between RV function and post-contrast T1 values supports that myocardial fibrosis is a causative factor of RV dysfunction in NICM, irrespective of RV afterload. This same structural milieu also appears integral to the propensity for both positive and negative RV remodeling long-term, suggestive that this is also determined by the degree of underlying RV fibrosis.

Reduced distortion artifact whole brain CBF mapping using blip-reversed non-segmented 3D echo planar imaging with pseudo-continuous arterial spin labeling.

PURPOSE: To implement and evaluate interleaved blip-up, blip-down, non-segmented 3D echo planar imaging (EPI) with pseudo-continuous arterial spin labeling (pCASL) and post-processing for reduced susceptibility artifact cerebral blood flow (CBF) maps. MATERIALS AND METHODS: 3D EPI non-segmented acquisition with a pCASL labeling sequence was modified to include alternating k-space coverage along phase encoding direction (referred to as "blip-reversed") for alternating dynamic acquisitions of control and label pairs. Eight volunteers were imaged on a 3T scanner. Images were corrected for distortion using spatial shifting transformation of the underlying field map. CBF maps were calculated and compared with maps obtained without blip reversal using matching gray matter (GM) images from a high resolution 3D scan. Additional benefit of using the correction for alternating blip-up and blip-down acquisitions was assessed by comparing to corrected blip-up only and corrected blip-down only CBF maps. Matched Student t-test of overlapping voxels for the eight volunteers was done to ascertain statistical improvement in distortion. RESULTS: Mean CBF value in GM for the eight volunteers from distortion corrected CBF maps was 50.8±9.9ml/min/100 gm tissue. Corrected CBF maps had 6.3% and 4.1% more voxels in GM when compared with uncorrected blip up (BU) and blip down (BD) images, respectively. Student t-test showed significant reduction in distortion when compared with blip-up images and blip-down images (p<0.001). When compared with corrected BU and corrected BD only CBF maps, BU and BD corrected maps had 2.3% and 1% more voxels (p=0.006 and 0.04, respectively). CONCLUSION: Pseudo-continuous arterial spin labeling with non-segmented 3D EPI acquisition using alternating blip-reversed k-space traversal and distortion correction provided significantly better matching GM CBF maps. In addition, employing alternating blip-reversed acquisitions during pCASL acquisition resulted in statistically significant improvement over corrected blip-up and blip-down CBF maps.

Long T2 suppression in native lung 3-D imaging using k-space reordered inversion recovery dual-echo ultrashort echo time MRI.

OBJECTIVE: Long T2 species can interfere with visualization of short T2 tissue imaging. For example, visualization of lung parenchyma can be hindered by breathing artifacts primarily from fat in the chest wall. The purpose of this work was to design and evaluate a scheme for long T2 species suppression in lung parenchyma imaging using 3-D inversion recovery double-echo ultrashort echo time imaging with a k-space reordering scheme for artifact suppression. MATERIALS AND METHODS: A hyperbolic secant (HS) pulse was evaluated for different tissues (T1/T2). Bloch simulations were performed with the inversion pulse followed by segmented UTE acquisition. Point spread function (PSF) was simulated for a standard interleaved acquisition order and a modulo 2 forward-reverse acquisition order. Phantom and in vivo images (eight volunteers) were acquired with both acquisition orders. Contrast to noise ratio (CNR) was evaluated in in vivo images prior to and after introduction of the long T2 suppression scheme. RESULTS: The PSF as well as phantom and in vivo images demonstrated reduction in artifacts arising from k-space modulation after using the reordering scheme. CNR measured between lung and fat and lung and muscle increased from -114 and -148.5 to +12.5 and 2.8 after use of the IR-DUTE sequence. Paired t test between the CNRs obtained from UTE and IR-DUTE showed significant positive change (p < 0.001 for lung-fat CNR and p = 0.03 for lung-muscle CNR). CONCLUSION: Full 3-D lung parenchyma imaging with improved positive contrast between lung and other long T2 tissue types can be achieved robustly in a clinically feasible time using IR-DUTE with image subtraction when segmented radial acquisition with k-space reordering is employed.

Submillimeter diffusion tensor imaging and late gadolinium enhancement cardiovascular magnetic resonance of chronic myocardial infarction.

BACKGROUND: Knowledge of the three-dimensional (3D) infarct structure and fiber orientation remodeling is essential for complete understanding of infarct pathophysiology and post-infarction electromechanical functioning of the heart. Accurate imaging of infarct microstructure necessitates imaging techniques that produce high image spatial resolution and high signal-to-noise ratio (SNR). The aim of this study is to provide detailed reconstruction of 3D chronic infarcts in order to characterize the infarct microstructural remodeling in porcine and human hearts. METHODS: We employed a customized diffusion tensor imaging (DTI) technique in conjunction with late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) on a 3T clinical scanner to image, at submillimeter resolution, myofiber orientation and scar structure in eight chronically infarcted porcine hearts ex vivo. Systematic quantification of local microstructure was performed and the chronic infarct remodeling was characterized at different levels of wall thickness and scar transmurality. Further, a human heart with myocardial infarction was imaged using the same DTI sequence. RESULTS: The SNR of non-diffusion-weighted images was >100 in the infarcted and control hearts. Mean diffusivity and fractional anisotropy (FA) demonstrated a 43% increase, and a 35% decrease respectively, inside the scar tissue. Despite this, the majority of the scar showed anisotropic structure with FA higher than an isotropic liquid. The analysis revealed that the primary eigenvector orientation at the infarcted wall on average followed the pattern of original fiber orientation (imbrication angle mean: 1.96 ± 11.03° vs. 0.84 ± 1.47°, p = 0.61, and inclination angle range: 111.0 ± 10.7° vs. 112.5 ± 6.8°, p = 0.61, infarcted/control wall), but at a higher transmural gradient of inclination angle that increased with scar transmurality (r = 0.36) and the inverse of wall thickness (r = 0.59). Further, the infarcted wall exhibited a significant increase in both the proportion of left-handed epicardial eigenvectors, and in the angle incoherency. The infarcted human heart demonstrated preservation of primary eigenvector orientation at the thinned region of infarct, consistent with the findings in the porcine hearts. CONCLUSIONS: The application of high-resolution DTI and LGE-CMR revealed the detailed organization of anisotropic infarct structure at a chronic state. This information enhances our understanding of chronic post-infarction remodeling in large animal and human hearts.

Three-dimensional T1 and T2* mapping of human lung parenchyma using interleaved saturation recovery with dual echo ultrashort echo time imaging (ITSR-DUTE).

PURPOSE: To develop and assess a new technique for three-dimensional (3D) full lung T1 and T2* mapping using a single free breathing scan during a clinically feasible time. MATERIALS AND METHODS: A 3D stack of dual-echo ultrashort echo time (UTE) radial acquisition interleaved with and without a WET (water suppression enhanced through T1 effects) saturation pulse was used to map T1 and T2* simultaneously in a single scan. Correction for modulation due to multiple views per segment was derived. Bloch simulations were performed to study saturation pulse excitation profile on lung tissue. Optimization of the saturation delay time (for T1 mapping) and echo time (for T2* mapping) was performed. Monte Carlo simulation was done to predict accuracy and precision of the sequence with signal-to-noise ratio of in vivo images used in the simulation. A phantom study was carried out using the 3D interleaved saturation recovery with dual echo ultrashort echo time imaging (ITSR-DUTE) sequence and reference standard inversion recovery spin echo sequence (IR-SE) to compare accuracy of the sequence. Nine healthy volunteers were imaged and mean (SD) of T1 and T2* in lung parenchyma at 3T were estimated through manually assisted segmentation. 3D lung coverage with a resolution of 2.5 × 2.5 × 6 mm3 was performed and nominal scan time was recorded for the scans. Repeatability was assessed in three of the volunteers. Regional differences in T1/T2* values were also assessed. RESULTS: The phantom study showed accuracy of T1 values to be within 2.3% of values obtained from IR-SE. Mean T1 value in lung parenchyma was 1002 ± 82 ms while T2* was 0.85 ± 0.1 ms. Scan time was ∼10 min for volunteer scans. Mean coefficient of variation (CV) across slices was 0.057 and 0.09, respectively. Regional variation along the gravitational direction and between right and left lung were not significant (P = 0.25 and P = 0.06, respectively) for T1. T2* showed significant variation (P = 0.03) along the gravitational direction. Repeatability for three volunteers was within 0.7% for T1 and 1.9% for T2*. CONCLUSION: 3D T1 and T2* maps of the entire lung can be obtained in a single scan of ∼10 min with a resolution of 2.5 × 2.5 × 6 mm3 . LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:1097-1104.

Structural and Functional Correlates of Myocardial T1 Mapping in 321 Patients With Hypertrophic Cardiomyopathy.

OBJECTIVE: The aim of this study was to evaluate the structural and functional correlates of T1 mapping in 321 patients with hypertrophic cardiomyopathy (HCM). METHODS: Three hundred twenty-one patients with HCM who underwent cardiac magnetic resonance from 2003 to 2013 were retrospectively identified from our institution's HCM registry. Left ventricular volume, function, late gadolinium enhancement (LGE), and Look-Locker T1 time were quantified. T1 time was normalized to blood pool to calculate T1 ratio. Correlations between LGE%, T1 ratio, and structural and functional features were performed using Pearson correlation coefficient. RESULTS: Late gadolinium enhancement showed stronger correlation with left ventricular mass index (r = 0.41, P < 0.001) compared with T1 ratio (r = -0.17, P = 0.004). Both LGE% and T1 ratio correlated with ejection fraction (r = -0.18 and P = 0.002 vs r = 0.21 and P < 0.001, respectively). E/e' showed correlation with LGE% but not with T1 ratio. CONCLUSIONS: Late gadolinium enhancement was more strongly correlated with the phenotypic expression of HCM compared with T1 ratio.

Focal fibrosis and diffuse fibrosis are predictors of reversed left ventricular remodeling in patients with non-ischemic cardiomyopathy.

BACKGROUND: Prognostic value of myocardial fibrosis in patients with non-ischemic idiopathic dilated cardiomyopathy (DCM) is not well-defined. We sought to assess the association of focal and diffuse myocardial fibrosis with left ventricular reversed remodeling (LVRR). METHODS: Patients with DCM who underwent cardiac MRI with baseline and subsequent follow-up echocardiography were included in the study. Post-contrast T1 times were corrected for renal function, body size, gadolinium dose and time after Gadolinium injection. Patients were followed over a median time of 29months to evaluate changes of left ventricular end-systolic volume (LVESV). A Linear Mixed Model was used to assess the relationship between the LVESV during follow-up, corrected post-T1 value delayed hyperenhancement (DHE), and modified Seattle Heart Failure Score (SHFS). RESULTS: A total of 103 patients (mean age 51±15years, 61% male) were evaluated. The mean LVEF was 33±11%, LVESVi 62±39ml/m(2), and T1 time 416±98. DHE was identified in 45 patients (44%). Patients with focal DHE (n=45) had higher LVESVi at baseline and during follow-up (p=0.024). Post T1 value >450 was an independent predictor of LVRR at the follow-up (Δ=24.6ml/m(2) SE 14.6ml/2, p=0.0480) in patients despite the presence of DHE, even after adjusting for their SHFS. CONCLUSION: While DCM patients with focal DHE demonstrated greater adverse LV remodeling than those without focal fibrosis, diffuse fibrosis independently predicts LVRR in DCM patients in patients despite the presence of focal fibrosis.

Myofiber Architecture of the Human Atria as Revealed by Submillimeter Diffusion Tensor Imaging.

BACKGROUND: Accurate knowledge of the human atrial fibrous structure is paramount in understanding the mechanisms of atrial electric function in health and disease. Thus far, such knowledge has been acquired from destructive sectioning, and there is a paucity of data about atrial fiber architecture variability in the human population. METHODS AND RESULTS: In this study, we have developed a customized 3-dimensional diffusion tensor magnetic resonance imaging sequence on a clinical scanner that makes it possible to image an entire intact human heart specimen ex vivo at submillimeter resolution. The data from 8 human atrial specimens obtained with this technique present complete maps of the fibrous organization of the human atria. The findings demonstrate that the main features of atrial anatomy are mostly preserved across subjects although the exact location and orientation of atrial bundles vary. Using the full tractography data, we were able to cluster, visualize, and characterize the distinct major bundles in the human atria. Furthermore, quantitative characterization of the fiber angles across the atrial wall revealed that the transmural fiber angle distribution is heterogeneous throughout different regions of the atria. CONCLUSIONS: The application of submillimeter diffusion tensor magnetic resonance imaging provides an unprecedented level of information on both human atrial structure, as well as its intersubject variability. The high resolution and fidelity of this data could enhance our understanding of structural contributions to atrial rhythm and pump disorders and lead to improvements in their targeted treatment.

Dose correction for post-contrast T1 mapping of the heart: the MESA study.

Post-contrast myocardial T1 (T1(myo,c)) values have been shown to be sensitive to myocardial fibrosis. Recent studies have shown differences in results obtained from T1(myo,c) and extracellular volume fraction (ECV) with respect to percentage fibrosis. By exploring the relationship between blood plasma volume and T1(myo,c), the underlying basis for the divergence can be explained. Furthermore, dose administration based on body mass index (BMI), age and gender can mitigate the divergence in results. Inter-subject comparison of T1(myo,c) required adjustment for dose (in mmol/kg), time and glomerular filtration rate. Further adjustment for effective dose based on lean muscle mass reflected by blood/plasma volume was performed. A test case of 605 subjects from the MESA study who had undergone pre- and post-contrast T1 mapping was studied. T1(myo,c) values were compared between subjects with and without metabolic syndrome (MetS), between smoking and non-smoking subjects, and subjects with and without impaired glucose tolerance, before and after dose adjustment based on plasma volume. Comparison with ECV (which is dose independent), pre-contrast myocardial T1 and blood normalized myocardial T1 values was also performed to validate the correction. There were significant differences in T1(myo,c) (post plasma volume correction) and ECV between current and former smokers (p value 0.017 and 0.01, respectively) but not T1(myo,c) prior to correction (p = 0.12). Prior to dose adjustment for plasma volume, p value was <0.001 for T1(myo,c) between MetS and non-MetS groups and was 0.13 between subjects with and without glucose intolerance; after adjustment for PV, p value was 0.63 and 0.99. Corresponding ECV p values were 0.44 and 0.99, respectively. Overall, ECV results showed the best agreement with PV corrected T1(myo,c) (mean absolute difference in p values = 0.073) and pre-contrast myocardial T1 in comparison with other measures (T1(myo,c( prior to correction, blood/plasma T1 value normalized myocardium). Weight-based contrast dosing administered in mmol/kg results in a bias in T1 values which can lead to erroneous conclusions. After adjustment for lean muscle mass based on plasma volume, results from T1(myo,c) were in line with ECV derived results. Furthermore, the use of a modified equivalent dose adjusted for BMI, age, sex and hematocrit can be adopted for quantitative imaging.

Evaluation of optimized breath-hold and free-breathing 3D ultrashort echo time contrast agent-free MRI of the human lung.

PURPOSE: To evaluate an optimized stack of radials ultrashort echo time (UTE) 3D magnetic resonance imaging (MRI) sequence for breath-hold and free-breathing imaging of the human lung. MATERIALS AND METHODS: A 3D stack of ultrashort echo time radials trajectory was optimized for coronal and axial lower-resolution breath-hold and higher-resolution free-breathing scans using Bloch simulations. The sequence was evaluated in 10 volunteers, without the use of contrast agents. Signal-to-noise ratio (SNR) mean and 95% confidence interval (CI) were determined from separate signal and noise images in a semiautomated fashion. The four scanning schemes were evaluated for significant differences in image quality using Student's t-test. Ten clinical patients were scanned with the sequence and findings were compared with concomitant computed tomography (CT) in nine patients. Breath-hold 3D spokes images were compared with 3D stack of radials in five volunteers. A Mann-Whitney U-test was performed to test significance in both cases. RESULTS: Breath-hold imaging of the entire lung in volunteers was performed with SNR (mean = 42.5 [CI]: 35.5-49.5; mean = 34.3 [CI]: 28.6-40) in lung parenchyma for coronal and axial scans, respectively, which can be used as a quick scout scan. Longer respiratory triggered free-breathing scan enabled high-resolution UTE scanning with mean SNR of 14.2 ([CI]: 12.9-15.5) and 9.2 ([CI]: 8.2-10.2) for coronal and axial scans, respectively. Axial free-breathing scans showed significantly higher image quality (P = 0.008) than the three other scanning schemes. The mean score for comparison with CT was 1.67 (score 0: n = 0; 1: n = 3; 2: n = 6). There was no significant difference between CT and MRI (P = 0.25). 3D stack of radials images were significantly better than 3D spokes images (P < 0.001). CONCLUSION: The optimized 3D stack of radials trajectory was shown to provide high-quality MR images of the lung parenchyma without the use of MRI contrast agents. The sequence may offer the possibility of breath-hold imaging and provides greater flexibility in trading off slice thickness and parallel imaging for scan time.

Part 1 - Coronary angiography with gadofosveset trisodium: a prospective feasibility study evaluating injection techniques for steady-state imaging.

BACKGROUND: The purpose of this study was to define an optimal injection protocol for 5-10 min duration navigator-based coronary MR angiography using an intravascular gadolinium-based contrast agent (GBCA), which is better suited for steady-state coronary MR angiography than conventional GBCAs. METHODS: Using projections from pharmacokinetic models of the intravascular concentration of gadofosveset, a dual-injection protocol was formulated and tested on 14 healthy human subjects. Modified Look-Locker inversion recovery (MOLLI) sequences were used for T1 mapping at 3 Tesla to evaluate the concentration of tracer in the aorta over the scanning interval. RESULTS: Pharmacokinetic models for a bolus plus slow infusion technique at a 5, 10, and 15 min steady state intravascular concentration was compared to single bolus curves. The 70 %/30 % bolus/slow infusion technique resulted in the highest intravascular concentration over a 5 min scan duration. Similarly, the 60 %/40 % bolus/slow infusion technique was projected to be ideal for image acquisition duration of 5-10 min. These models were confirmed with T1 maps on normal volunteers. Arterial-venous mixing of contrast was achieved within 90 s of the beginning of the bolus. CONCLUSIONS: Gadofosveset injection is optimized for the lowest intravascular T1 time for 5-10 min duration MR angiography by bolus injection of 60-70 % of the total dose followed by slow infusion of the remainder of the total dose. This protocol achieves rapid and prolonged steady state intravascular concentrations of the GBCA that may be useful for prolonged image acquisition, such as required for navigator-based coronary MR angiography at 3 Tesla. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01130545 NCT01130545 , registered as of May 25, 2010.