Matthew D. Robson

Magnetic resonance: an introduction to ultrashort TE (UTE) imaging.

The background underpinning the clinical use of ultrashort echo-time (UTE) pulse sequences for imaging tissues or tissue components with short T2s is reviewed. Tissues properties are discussed, and tissues are divided into those with a majority of short T2 relaxation components and those with a minority. Features of the basic physics relevant to UTE imaging are described including the fact that when the radiofrequency pulse duration is of the order T2, rotation of tissue magnetization into the transverse plane is incomplete. Consequences of the broad line-width of short T2 components are also discussed including their partial saturation by off-resonance fat suppression pulses as well as multislice and multiecho imaging. The need for rapid data acquisition of the order T2 is explained. The basic UTE pulse sequence with its half excitation pulse and radial imaging from the center of k-space is described together with options that suppress fat and/or long T2 components. Image interpretation is discussed. Clinical features of the imaging of cortical bone, tendons, ligaments, menisci, and periosteum as well as brain, liver, and spine are illustrated. Short T2 components in all of these tissues may show high signals. Possible future developments are outlined as are technical limitations.

Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement

Rapid innovations in cardiovascular magnetic resonance (CMR) now permit the routine acquisition of quantitative measures of myocardial and blood T1 which are key tissue characteristics. These capabilities introduce a new frontier in cardiology, enabling the practitioner/investigator to quantify biologically important myocardial properties that otherwise can be difficult to ascertain clinically. CMR may be able to track biologically important changes in the myocardium by: a) native T1 that reflects myocardial disease involving the myocyte and interstitium without use of gadolinium based contrast agents (GBCA), or b) the extracellular volume fraction (ECV)–a direct GBCA-based measurement of the size of the extracellular space, reflecting interstitial disease. The latter technique attempts to dichotomize the myocardium into its cellular and interstitial components with estimates expressed as volume fractions. This document provides recommendations for clinical and research T1 and ECV measurement, based on published evidence when available and expert consensus when not. We address site preparation, scan type, scan planning and acquisition, quality control, visualisation and analysis, technical development. We also address controversies in the field. While ECV and native T1 mapping appear destined to affect clinical decision making, they lack multi-centre application and face significant challenges, which demand a community-wide approach among stakeholders. At present, ECV and native T1 mapping appear sufficiently robust for many diseases; yet more research is required before a large-scale application for clinical decision-making can be recommended.

Normal Human Left and Right Ventricular and Left Atrial Dimensions Using Steady State Free Precession Magnetic Resonance Imaging

PURPOSE The aim of this project was to establish a database of left and right ventricular and left atrial dimensions in healthy volunteers using steady-state free precession cardiac magnetic resonance imaging, the clinical technique of choice, across a wide age range. METHODS 108 healthy volunteers (63 male, 45 female) underwent cardiac magnetic resonance imaging using steady-state free precession sequences. Manual analysis was performed by 2 experienced observers. RESULTS Left and right ventricular volumes and left ventricular mass were larger in males than females: LV end-diastolic volume 160 +/- 29 mL vs. 135 +/- 26 mL, LV end-systolic volume 50 +/- 16 mL vs. 42 +/- 12 mL; RV end-diastolic volume 190 +/- 33 mL vs. 148 +/- 35 mL, RV end-systolic volume 78 +/- 20 mL vs. 56 +/- 18 mL (p < .05 for all). Normalization of values to body surface area removed the statistical differences for LV volumes, but not for LV mass or RV volumes. With increased age, males showed a significant decrease in volume and mass indices for both ventricles, while female values remained unchanged. Compared to females, males had significantly larger maximal left atrial volumes (103 +/- 30 mL vs. 89 +/- 21 mL, p = .01) and left atrial stroke volumes (58 +/- 23 mL vs. 48 +/- 15 mL, p = .01). There was no difference in left atrial ejection fraction between the sexes. CONCLUSION We have produced a large database of age-related normal ranges for left and right ventricular function and left atrial function in males and females. This will allow accurate interpretation of clinical and research datasets.

Shortened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical myocardial T1-mapping at 1.5 and 3 T within a 9 heartbeat breathhold

BackgroundT1 mapping allows direct in-vivo quantitation of microscopic changes in the myocardium, providing new diagnostic insights into cardiac disease. Existing methods require long breath holds that are demanding for many cardiac patients. In this work we propose and validate a novel, clinically applicable, pulse sequence for myocardial T1-mapping that is compatible with typical limits for end-expiration breath-holding in patients.Materials and methodsThe Shortened MOdified Look-Locker Inversion recovery (ShMOLLI) method uses sequential inversion recovery measurements within a single short breath-hold. Full recovery of the longitudinal magnetisation between sequential inversion pulses is not achieved, but conditional interpretation of samples for reconstruction of T1-maps is used to yield accurate measurements, and this algorithm is implemented directly on the scanner. We performed computer simulations for 100 ms<T1 < 2.7 s and heart rates 40-100 bpm followed by phantom validation at 1.5T and 3T. In-vivo myocardial T1-mapping using this method and the previous gold-standard (MOLLI) was performed in 10 healthy volunteers at 1.5T and 3T, 4 volunteers with contrast injection at 1.5T, and 4 patients with recent myocardial infarction (MI) at 3T.ResultsWe found good agreement between the average ShMOLLI and MOLLI estimates for T1 < 1200 ms. In contrast to the original method, ShMOLLI showed no dependence on heart rates for long T1 values, with estimates characterized by a constant 4% underestimation for T1 = 800-2700 ms. In-vivo, ShMOLLI measurements required 9.0 ± 1.1 s (MOLLI = 17.6 ± 2.9 s). Average healthy myocardial T1 s by ShMOLLI at 1.5T were 966 ± 48 ms (mean ± SD) and 1166 ± 60 ms at 3T. In MI patients, the T1 in unaffected myocardium (1216 ± 42 ms) was similar to controls at 3T. Ischemically injured myocardium showed increased T1 = 1432 ± 33 ms (p < 0.001). The difference between MI and remote myocardium was estimated 15% larger by ShMOLLI than MOLLI (p < 0.04) which suffers from heart rate dependencies for long T1. The in-vivo variability within ShMOLLI T1-maps was only 14% (1.5T) or 18% (3T) higher than the MOLLI maps, but the MOLLI acquisitions were twice longer than ShMOLLI acquisitions.ConclusionShMOLLI is an efficient method that generates immediate, high-resolution myocardial T1-maps in a short breath-hold with high precision. This technique provides a valuable clinically applicable tool for myocardial tissue characterisation.

Quantitative investigation of connections of the prefrontal cortex in the human and macaque using probabilistic diffusion tractography

The functions of prefrontal cortex (PFC) areas are constrained by their anatomical connections. There is little quantitative information about human PFC connections, and, instead, our knowledge of primate PFC connections is derived from tracing studies in macaques. The connections of subcortical areas, in which white matter penetration and hence diffusion anisotropy are greatest, can be studied with diffusion-weighted imaging (DWI) tractography. We therefore used DWI tractography in four macaque and 10 human hemispheres to compare the connections of PFC regions with nine subcortical regions, including several fascicles and several subcortical nuclei. A distinct connection pattern was identified for each PFC and each subcortical region. Because some of the fascicles contained connections with posterior cortical areas, it was also possible to draw inferences about PFC connection patterns with posterior cortical areas. Notably, it was possible to identify similar circuits centered on comparable PFC regions in both species; PFC regions probably engage in similar patterns of regionally specific functional interaction with other brain areas in both species. In the case of one area traditionally assigned to the human PFC, the pars opercularis, the distribution of connections was not reminiscent of any macaque PFC region but, instead, resembled the pattern for macaque ventral premotor area. Some limitations to the DWI approach were apparent; the high diffusion anisotropy in the corpus callosum made it difficult to compare connection probability values in the adjacent cingulate region.

Noncontrast T1 mapping for the diagnosis of cardiac amyloidosis.

OBJECTIVES This study sought to explore the potential role of noncontrast myocardial T1 mapping for detection of cardiac involvement in patients with primary amyloid light-chain (AL) amyloidosis. BACKGROUND Cardiac involvement carries a poor prognosis in systemic AL amyloidosis. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is useful for the detection of cardiac amyloid, but characteristic LGE patterns do not always occur or they appear late in the disease. Noncontrast characterization of amyloidotic myocardium with T1 mapping may improve disease detection. Furthermore, quantitative assessment of myocardial amyloid load would be of great value. METHODS Fifty-three AL amyloidosis patients (14 with no cardiac involvement, 11 with possible involvement, and 28 with definite cardiac involvement based on standard biomarker and echocardiographic criteria) underwent CMR (1.5-T) including noncontrast T1 mapping (shortened modified look-locker inversion recovery [ShMOLLI] sequence) and LGE imaging. These were compared with 36 healthy volunteers and 17 patients with aortic stenosis and a comparable degree of left ventricular hypertrophy as the cardiac amyloid patients. RESULTS Myocardial T1 was significantly elevated in cardiac AL amyloidosis patients (1,140 ± 61 ms) compared to normal subjects (958 ± 20 ms, p < 0.001) and patients with aortic stenosis (979 ± 51 ms, p < 0.001). Myocardial T1 was increased in AL amyloid even when cardiac involvement was uncertain (1,048 ± 48 ms) or thought absent (1,009 ± 31 ms). A noncontrast myocardial T1 cutoff of 1,020 ms yielded 92% accuracy for identifying amyloid patients with possible or definite cardiac involvement. In the AL amyloidosis cohort, there were significant correlations between myocardial T1 time and indices of systolic and diastolic dysfunction. CONCLUSIONS Noncontrast T1 mapping has high diagnostic accuracy for detecting cardiac AL amyloidosis, correlates well with markers of systolic and diastolic dysfunction, and is potentially more sensitive for detecting early disease than LGE imaging. Elevated myocardial T1 may represent a direct marker of cardiac amyloid load. Further studies are needed to assess the prognostic significance of T1 elevation.

Non-contrast T1-mapping detects acute myocardial edema with high diagnostic accuracy: a comparison to T2-weighted cardiovascular magnetic resonance

BackgroundT2w-CMR is used widely to assess myocardial edema. Quantitative T1-mapping is also sensitive to changes in free water content. We hypothesized that T1-mapping would have a higher diagnostic performance in detecting acute edema than dark-blood and bright-blood T2w-CMR.MethodsWe investigated 21 controls (55 ± 13 years) and 21 patients (61 ± 10 years) with Takotsubo cardiomyopathy or acute regional myocardial edema without infarction. CMR performed within 7 days included cine, T1-mapping using ShMOLLI, dark-blood T2-STIR, bright-blood ACUT2E and LGE imaging. We analyzed wall motion, myocardial T1 values and T2 signal intensity (SI) ratio relative to both skeletal muscle and remote myocardium.ResultsAll patients had acute cardiac symptoms, increased Troponin I (0.15-36.80 ug/L) and acute wall motion abnormalities but no LGE. T1 was increased in patient segments with abnormal and normal wall motion compared to controls (1113 ± 94 ms, 1029 ± 59 ms and 944 ± 17 ms, respectively; p < 0.001). T2 SI ratio using STIR and ACUT2E was also increased in patient segments with abnormal and normal wall motion compared to controls (all p < 0.02). Receiver operator characteristics analysis showed that T1-mapping had a significantly larger area-under-the-curve (AUC = 0.94) compared to T2-weighted methods, whether the reference ROI was skeletal muscle or remote myocardium (AUC = 0.58-0.89; p < 0.03). A T1 value of greater than 990 ms most optimally differentiated segments affected by edema from normal segments at 1.5 T, with a sensitivity and specificity of 92 %.ConclusionsNon-contrast T1-mapping using ShMOLLI is a novel method for objectively detecting myocardial edema with a high diagnostic performance. T1-mapping may serve as a complementary technique to T2-weighted imaging for assessing myocardial edema in ischemic and non-ischemic heart disease, such as quantifying area-at-risk and diagnosing myocarditis.

Evidence for Microvascular Dysfunction in Hypertrophic Cardiomyopathy: New Insights From Multiparametric Magnetic Resonance Imaging

Background— Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) may create an ischemic substrate conducive to sudden death, but it remains unknown whether the extent of hypertrophy is associated with proportionally poorer perfusion reserve. Comparisons between magnitude of hypertrophy, impairment of perfusion reserve, and extent of fibrosis may offer new insights for future clinical risk stratification in HCM but require multiparametric imaging with high spatial and temporal resolution. Methods and Results— Degree of hypertrophy, myocardial blood flow at rest and during hyperemia (hMBF), and myocardial fibrosis were assessed with magnetic resonance imaging in 35 HCM patients (9 [26%] male/26 female) and 14 healthy controls (4 [29%] male/10 female), aged 18 to 78 years (mean±SD, 42±14 years) with the use of the American Heart Association left ventricular 16-segment model. Resting MBF was similar in HCM patients and controls. hMBF was lower in HCM patients (1.84±0.89 mL/min per gram) than in healthy controls (3.42±1.76 mL/min per gram, with a difference of −0.95±0.30 [SE] mL/min per gram; P<0.001) after adjustment for multiple variables, including end-diastolic segmental wall thickness (P<0.001). In HCM patients, hMBF decreased with increasing end-diastolic wall thickness (P<0.005) and preferentially in the endocardial layer. The frequency of endocardial hMBF falling below epicardial hMBF rose with wall thickness (P=0.045), as did the incidence of fibrosis (P<0.001). Conclusions— In HCM the vasodilator response is reduced, particularly in the endocardium, and in proportion to the magnitude of hypertrophy. Microvascular dysfunction and subsequent ischemia may be important components of the risk attributable to HCM.

Effects of High-Dose Modified-Release Nicotinic Acid on Atherosclerosis and Vascular Function: A Randomized, Placebo-Controlled, Magnetic Resonance Imaging Study

OBJECTIVES Our aim was to determine the effects of high-dose (2 g) nicotinic acid (NA) on progression of atherosclerosis and measures of vascular function. BACKGROUND NA raises high-density lipoprotein cholesterol (HDL-C) and reduces low-density lipoprotein cholesterol and is widely used as an adjunct to statin therapy in patients with coronary artery disease. Although changes in plasma lipoproteins suggest potential benefit, there is limited evidence of the effects of NA on disease progression when added to contemporary statin treatment. METHODS We performed a double-blind, randomized, placebo-controlled study of 2 g daily modified-release NA added to statin therapy in 71 patients with low HDL-C (<40 mg/dl) and either: 1) type 2 diabetes with coronary heart disease; or 2) carotid/peripheral atherosclerosis. The primary end point was the change in carotid artery wall area, quantified by magnetic resonance imaging, after 1 year. RESULTS NA increased HDL-C by 23% and decreased low-density lipoprotein cholesterol by 19%. At 12 months, NA significantly reduced carotid wall area compared with placebo (adjusted treatment difference: -1.64 mm(2) [95% confidence interval: -3.12 to -0.16]; p = 0.03). Mean change in carotid wall area was -1.1 +/- 2.6 mm(2) for NA versus +1.2 +/- 3.0 mm(2) for placebo. In both the treatment and placebo groups, larger plaques were more prone to changes in size (r = 0.4, p = 0.04 for placebo, and r = -0.5, p = 0.02 for NA). CONCLUSIONS In statin-treated patients with low HDL-C, high-dose modified-release NA, compared with placebo, significantly reduces carotid atherosclerosis within 12 months. (Oxford Niaspan Study: Effects of Niaspan on Atherosclerosis and Endothelial Function; NCT00232531).

Human non-contrast T1 values and correlation with histology in diffuse fibrosis

Background Aortic stenosis (AS) leads to diffuse fibrosis in the myocardium, which is linked to adverse outcome. Myocardial T1 values change with tissue composition. Objective To test the hypothesis that our recently developed non-contrast cardiac magnetic resonance (CMR) T1 mapping sequence could identify myocardial fibrosis without contrast agent. Design, setting and patients A prospective CMR non-contrast T1 mapping study of 109 patients with moderate and severe AS and 33 age- and gender-matched controls. Methods CMR at 1.5 T, including non-contrast T1 mapping using a shortened modified Look–Locker inversion recovery sequence, was carried out. Biopsy samples for histological assessment of collagen volume fraction (CVF%) were obtained in 19 patients undergoing aortic valve replacement. Results There was a significant correlation between T1 values and CVF% (r=0.65, p=0.002). Mean T1 values were significantly longer in all groups with severe AS (972±33 ms in severe asymptomatic, 1014±38 ms in severe symptomatic) than in normal controls (944±16 ms) (p<0.05). The strongest associations with T1 values were for aortic valve area (r=−0.40, p=0.001) and left ventricular mass index (LVMI) (r=0.36, p=0.008), and these were the only independent predictors on multivariate analysis. Conclusions Non-contrast T1 values are increased in patients with severe AS and further increase in symptomatic compared with asymptomatic patients. T1 values lengthened with greater LVMI and correlated with the degree of biopsy-quantified fibrosis. This may provide a useful clinical assessment of diffuse myocardial fibrosis in the future.