Coronary endothelial function (endoFx) is abnormal in patients with established coronary artery disease (CAD) and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the non-invasive assessment of both anatomic and functional (endoFx) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endoFx is related to measures of early atherosclerosis such as increased coronary wall thickness (CWT).
Methods and Results
Seventeen arteries in fourteen healthy adults and seventeen arteries in fourteen patients with non-obstructive CAD were studied. To measure endoFx, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor and changes in coronary cross-sectional area (CSA) and flow were measured. Black blood imaging was performed to quantify CWT and other indices of arterial remodeling. The mean stress-induced change in CSA was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2±6.8%, p<0.0001, n=17). Mean CWT was lower in healthy subjects (0.9±0.2mm) than in CAD patients (1.4±0.3mm, p<0.0001). In contrast to healthy subjects, stress-induced changes in CSA, a measure of coronary endoFx, correlated inversely with CWT in CAD patients (r= -0.73, p=0.0008).
There is an inverse relationship between coronary endothelial function and local CWT in CAD patients but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease.
coronary disease; endothelium; magnetic resonance imaging
Speed and signal-to-noise ratio (SNR) are critical for localized magnetic resonance spectroscopy (MRS) of low-concentration metabolites. Matching voxels to anatomical compartments a priori yields better SNR than the spectra created by summing signals from constituent chemical-shift-imaging (CSI) voxels post-acquisition. Here, a new method of localized Spectroscopy using Linear Algebraic Modeling (SLAM) is presented, that can realize this additional SNR gain. Unlike prior methods, SLAM generates spectra from C signal-generating anatomic compartments utilizing a CSI sequence wherein essentially only the C central k-space phase-encoding gradient steps with highest SNR are retained. After MRI-based compartment segmentation, the spectra are reconstructed by solving a sub-set of linear simultaneous equations from the standard CSI algorithm. SLAM is demonstrated with one-dimensional CSI surface coil phosphorus MRS in phantoms, the human leg and the heart on a 3T clinical scanner. Its SNR performance, accuracy, sensitivity to registration errors and inhomogeneity, are evaluated. Compared to one-dimensional CSI, SLAM yielded quantitatively the same results 4-times faster in 24 cardiac patients and healthy subjects. SLAM is further extended with fractional phase-encoding gradients that optimize SNR and/or minimize both inter- and intra-compartmental contamination. In proactive cardiac phosphorus MRS of 6 healthy subjects, both SLAM and fractional-SLAM (fSLAM) produced results indistinguishable from CSI while preserving SNR gains of 36–45% in the same scan-time. Both SLAM and fSLAM are simple to implement and reduce the minimum scan-time for CSI, which otherwise limits the translation of higher SNR achievable at higher field strengths to faster scanning.
spectral localization; chemical shift imaging (CSI); cardiac; constrained reconstruction; phosphorus; metabolism; heart
Our objective is to test the hypothesis that coronary endothelial function (CorEndoFx) does not change with repeated isometric handgrip (IHG) stress in CAD patients or healthy subjects.
Coronary responses to endothelial-dependent stressors are important measures of vascular risk that can change in response to environmental stimuli or pharmacologic interventions. The evaluation of the effect of an acute intervention on endothelial response is only valid if the measurement does not change significantly in the short term under normal conditions. Using 3.0 Tesla (T) MRI, we non-invasively compared two coronary artery endothelial function measurements separated by a ten minute interval in healthy subjects and patients with coronary artery disease (CAD).
Twenty healthy adult subjects and 12 CAD patients were studied on a commercial 3.0 T whole-body MR imaging system. Coronary cross-sectional area (CSA), peak diastolic coronary flow velocity (PDFV) and blood-flow were quantified before and during continuous IHG stress, an endothelial-dependent stressor. The IHG exercise with imaging was repeated after a 10 minute recovery period.
In healthy adults, coronary artery CSA changes and blood-flow increases did not differ between the first and second stresses (mean % change ±SEM, first vs. second stress CSA: 14.8%±3.3% vs. 17.8%±3.6%, p = 0.24; PDFV: 27.5%±4.9% vs. 24.2%±4.5%, p = 0.54; blood-flow: 44.3%±8.3 vs. 44.8%±8.1, p = 0.84). The coronary vasoreactive responses in the CAD patients also did not differ between the first and second stresses (mean % change ±SEM, first stress vs. second stress: CSA: −6.4%±2.0% vs. −5.0%±2.4%, p = 0.22; PDFV: −4.0%±4.6% vs. −4.2%±5.3%, p = 0.83; blood-flow: −9.7%±5.1% vs. −8.7%±6.3%, p = 0.38).
MRI measures of CorEndoFx are unchanged during repeated isometric handgrip exercise tests in CAD patients and healthy adults. These findings demonstrate the repeatability of noninvasive 3T MRI assessment of CorEndoFx and support its use in future studies designed to determine the effects of acute interventions on coronary vasoreactivity.
Magnetic resonance angiography (MRA) provides a noninvasive means to detect the presence, location and severity of atherosclerosis throughout the vascular system. In such studies, and especially those in the coronary arteries, the vessel luminal area is typically measured at multiple cross-sectional locations along the course of the artery. The advent of fast volumetric imaging techniques covering proximal to mid segments of coronary arteries necessitates automatic analysis tools requiring minimal manual interactions to robustly measure cross-sectional area along the three-dimensional track of the arteries in under-sampled and non-isotropic datasets. In this work, we present a modular approach based on level set methods to track the vessel centerline, segment the vessel boundaries, and measure transversal area using two user-selected endpoints in each coronary of interest. Arterial area and vessel length are measured using our method and compared to the standard Soap-Bubble reformatting and analysis tool in in-vivo non-contrast enhanced coronary MRA images.
3D Centerline Tracking; 3D Segmentation; Level Set Methods; Non-contrast enhanced Magnetic Resonance Angiography; Coronary Arteries
Coronary vessel distensibility is reduced with atherosclerosis and normal aging but direct measurements have historically required invasive measurements at cardiac catheterization. Therefore, we sought to assess coronary artery distensibility non-invasively with 3.0T coronary magnetic resonance imaging (MRI) and to test the hypothesis that this non-invasive technique can detect differences in coronary distensibility between healthy and coronary artery disease (CAD) subjects. Thirty-eight healthy, adult subjects (23 men, mean age 31±10 years) and 21 patients with CAD defined on X-ray angiography (11 men, mean age 57±6 years) were studied on a commercial whole-body MR imaging system (Achieva 3.0 T; Philips, Best, The Netherlands). In each subject, the proximal segment of a coronary artery was imaged for cross-sectional area measurements using cine spiral MRI. Distensibility (mmHg−1*103) was determined as: (end-systolic lumen area–end-diastolic lumen area) / (pulse pressure multiplied by the end-diastolic lumen area). Pulse pressure was calculated as the difference between the systolic and diastolic brachial blood pressures. Thirty-four healthy subjects and nineteen patients had adequate image quality for coronary area measurements. Coronary artery distensibility was significantly higher in healthy subjects, than in the CAD patients (mean ± 1 SD: 2.4 ± 1.7 mmHg−1*103 vs. 1.1 ± 1.1 mmHg−1*103 respectively, p=0.007); (median: 2.2 vs. 0.9 mmHg−1*103). In a subgroup of 10 CAD patients we found a significant correlation between coronary artery distensibility measurements assessed with MRI and X-ray coronary angiography (R=0.65; p=0.003). In a group of 10 healthy subjects repeated distensibility measurements demonstrated a significant correlation (R=0.80; p=0.006). In conclusion, 3.0T MRI, a reproducible non-invasive means to assess human coronary artery vessel wall distensibility, is able to detect significant differences in distensibility between healthy subjects and CAD patients.
coronary artery distensibility; non-invasive; cardiac magnetic resonance; 3.0 Tesla
To develop and evaluate a practical method for the quantification of signal-to-noise ratio (SNR) on coronary magnetic resonance angiograms (MRA) acquired with parallel imaging.
Materials and Methods
To quantify the spatially varying noise due to parallel imaging reconstruction, a new method has been implemented incorporating image data acquisition followed by a fast noise scan during which radiofrequency pulses, cardiac triggering and navigator gating are disabled. The performance of this method was evaluated in a phantom study where SNR measurements were compared to those of a reference standard (multiple repetitions). Subsequently, SNR of myocardium and posterior skeletal muscle was determined on in vivo human coronary MRA.
In a phantom, the SNR measured using the proposed method deviated less than 10.1% from the reference method for small geometry factors (<=2). In-vivo, the noise scan for a 10 minutes coronary MRA acquisition was acquired in 30s. Higher signal and lower SNR, due to spatially varying noise, were found in myocardium compared to posterior skeletal muscle.
SNR quantification based on a fast noise scan is a validated and easy-to-use method when applied to 3D coronary MRA obtained with parallel imaging as long as the geometry factor remains low.
SNR measurement; parallel imaging; coronary MRA; phased array coils; image noise
The hypothesis that the failing heart may be energy starved is supported, in part, by observations of reduced rates of ATP synthesis through the creatine kinase (CK) reaction, the primary myocardial energy reservoir, in heart failure (HF) patients. Although murine models have been used to probe HF pathophysiology, it has not been possible to non-invasively measure the rate of ATP synthesis through CK in the in vivo mouse heart. The purpose of this work was to exploit non-invasive spatially-localized magnetic resonance spectroscopy (MRS) techniques to measure ATP flux through CK in in vivo mouse hearts and determine the extent of any reductions in murine HF.
Methods and Results
The Triple Repetition Time Saturation Transfer (TRiST) MRS method of measuring ATP kinetics was first validated in skeletal muscle, rendering similar results to conventional saturation transfer MRS. In normal mouse hearts the in vivo CK pseudo-first-order-rate constant, kf, was 0.32±0.03 s−1 (mean±SD) and the rate of ATP synthesis through CK was 3.16±0.47 µmol/g/s. Thoracic aortic constriction (TAC) reduced kf by 31% (0.23±0.03 s−1, p<0.0001) and ATP synthesis through CK by 51% (1.54±0.25 µmol/g/s, p<0.0001), analogous values to those in failing human hearts.
Despite the small size and high murine heart rate, the ATP synthesis rate through CK is similar in vivo in murine and human hearts and comparably reduced in HF. Because murine TAC shares fundamental energetic similarities with human HF, this model and new MRS approach promise a powerful means to non-invasively probe altered energetics in HF.
energetics; CK flux; hypertrophy; in vivo mouse hearts; magnetic resonance spectroscopy
Fast, minimally invasive, high-resolution intravascular imaging is essential for identifying vascular pathological features and for developing novel diagnostic tools and treatments. Intravascular magnetic resonance imaging (MRI) with active internal probes offers high sensitivity to pathological features without ionizing radiation or the limited luminal views of conventional X-rays, but has been unable to provide a high-speed, high-resolution, endoscopic view. Herein, real-time MRI endoscopy is introduced for performing MRI from a viewpoint intrinsically locked to a miniature active, internal transmitter–receiver in a clinical 3.0-TMRI scanner. Real-time MRI endoscopy at up to 2 frames/s depicts vascular wall morphological features, atherosclerosis, and calcification at 80 to 300 μm resolution during probe advancement through diseased human iliac artery specimens and atherosclerotic rabbit aortas in vivo. MRI endoscopy offers the potential for fast, minimally invasive, transluminal, high-resolution imaging of vascular disease on a common clinical platform suitable for evaluating and targeting atherosclerosis in both experimental and clinical settings.
atherosclerosis; calcium; endoscopy; intravascular; magnetic resonance imaging
The study was approved by the animal care and use committee. The purpose of the study was to prospectively establish proof of principle in vivo in canines for a magnetic resonance (MR) imaging–compatible robotic system designed for image-guided prostatic needle intervention. The entire robot is built with nonmagnetic and dielectric materials and in its current configuration is designed to perform fully automated brachytherapy seed placement within a closed MR imager. With a 3.0-T imager, in four dogs the median error for MR imaging–guided needle positioning and seed positioning was 2.02 mm (range, 0.86–3.18 mm) and 2.50 mm (range, 1.45–10.54 mm), respectively. The robotic system is capable of accurate MR imaging–guided prostatic needle intervention within a standard MR imager in vivo in a canine model.
Human cardiac phosphorus MR saturation transfer (ST) experiments to quantify creatine kinase (CK) forward rate constants (kf) have previously been performed at 1.5T. Such experiments could benefit from increased signal-to-noise ratio and spectral resolution at 3T. At 1.5T, the four-angle ST method was applied with low-angle adiabatic pulses and surface coils. However, low-angle adiabatic pulses are potentially problematic above 1.5T due to bandwidth limitations, power requirements, power deposition and intra-pulse spin-spin decay. For localized metabolite spin-lattice relaxation time (T1) measurements, a dual repetition time (2TR) approach with adiabatic half-passage pulses was recently introduced to solve these problems at 3T. Because the ST experiment requires a T1 measurement performed while one reacting moiety is saturated, we adapt the 2TR approach to measure kf using a Triple Repetition time ST (TRiST) method. A new pulsed saturation scheme with reduced sensitivity to static magnetic field inhomogeneity and compatibility with cardiac triggering is also presented. TRiST measurements of kf are validated in human calf muscle against conventional ST, and found to agree within 3%. The first 3T TRiST measurements of CK kf in the human calf (n=6), chest muscle and heart (n=8) are: 0.26±0.04s−1, 0.23±0.03s−1 and 0.32±0.07s−1, respectively, consistent with prior 1.5T values.
saturation transfer; human heart; metabolism; reaction rate; high-energy phosphate; saturation pulses; creatine kinase and 3 Tesla
Increased cardiac lipid content has been associated with diabetic cardiomyopathy. We recently showed that cardiac lipid content is reduced after 12 weeks of physical activity training in healthy overweight subjects. The beneficial effect of exercise training on cardiovascular risk is well established and the decrease in cardiac lipid content with exercise training in healthy overweight subjects was accompanied by improved ejection fraction. It is yet unclear whether diabetic patients respond similarly to physical activity training and whether a lowered lipid content in the heart is necessary for improvements in cardiac function. Here, we investigated whether exercise training is able to lower cardiac lipid content and improve cardiac function in type 2 diabetic patients.
Eleven overweight-to-obese male patients with type 2 diabetes mellitus (age: 58.4 ± 0.9 years, BMI: 29.9 ± 0.01 kg/m2) followed a 12-week training program (combination endurance/strength training, three sessions/week). Before and after training, maximal whole body oxygen uptake (VO2max) and insulin sensitivity (by hyperinsulinemic, euglycemic clamp) was determined. Systolic function was determined under resting conditions by CINE-MRI and cardiac lipid content in the septum of the heart by Proton Magnetic Resonance Spectroscopy.
VO2max increased (from 27.1 ± 1.5 to 30.1 ± 1.6 ml/min/kg, p = 0.001) and insulin sensitivity improved upon training (insulin stimulated glucose disposal (delta Rd of glucose) improved from 5.8 ± 1.9 to 10.3 ± 2.0 μmol/kg/min, p = 0.02. Left-ventricular ejection fraction improved after training (from 50.5 ± 2.0 to 55.6 ± 1.5%, p = 0.01) as well as cardiac index and cardiac output. Unexpectedly, cardiac lipid content in the septum remained unchanged (from 0.80 ± 0.22% to 0.95 ± 0.21%, p = 0.15).
Twelve weeks of progressive endurance/strength training was effective in improving VO2max, insulin sensitivity and cardiac function in patients with type 2 diabetes mellitus. However, cardiac lipid content remained unchanged. These data suggest that a decrease in cardiac lipid content in type 2 diabetic patients is not a prerequisite for improvements in cardiac function.
magnetic resonance spectroscopy; magnetic resonance imaging; ectopic fat; type 2 diabetes mellitus; exercise; cardiomyopathy; lipotoxicity
The paper presents a robotic method of performing low dose rate prostate brachytherapy under magnetic resonance imaging (MRI) guidance. The design and operation of a fully automated MR compatible seed injector is presented. This is used with the MrBot robot for transperineal percutaneous prostate access. A new image-registration marker and algorithms are also presented. The system is integrated and tested with a 3T MRI scanner. Tests compare three different registration methods, assess the precision of performing automated seed deployment, and use the seeds to assess the accuracy of needle targeting under image guidance. Under the ideal conditions of the in vitro experiments, results show outstanding image-guided needle and seed placement accuracy.
Brachytherapy; IGI; image-guided robot; MR Compatible
Cardiac phosphorus magnetic resonance spectroscopy (MRS) with surface coils promises better quantification at 3T due to improved signal-to-noise ratios and spectral resolution compared to 1.5T. However, Bloch equation and field analyses at 3T show that for efficient quantitative MRS protocols employing small-angle adiabatic (BIR4/BIRP) pulses the excitation-field is limited by RF power requirements and power deposition. When BIR4/BIRP pulse duration is increased to reduce power levels, T2-decay can introduce flip-angle dependent errors in the steady-state magnetization, causing errors in saturation corrections for metabolite quantification and in T1s measured by varying the flip-angle. A new dual-repetition-time (2TR) T1 method using frequency-sign-cycled adiabatic-half-passage pulses is introduced to alleviate power requirements, and avoid the problem related to T2 relaxation during the RF pulse. The 2TR method is validated against inversion-recovery in phantoms using a practical transmit/receive coil set designed for phosphorus MRS of the heart at depths of 9-10 cm with 4kW of pulse power. The T1s of phosphocreatine (PCr) and adenosine triphosphate (γ-ATP) in the calf-muscle (n=9) at 3T are 6.8±0.3s and 5.4±0.6s respectively. For heart (n=10) the values are 5.8±0.5s (PCr) and 3.1±0.6s (γ-ATP). The 2TR protocol measurements agreed with those obtained by conventional methods to within 10%.
phosphorus MRS; human heart; human muscle; metabolism; spin-lattice relaxation (T1); adiabatic pulses; 3 Tesla
High field (≥3T) cardiac MRI is challenged by inhomogeneities of both the static magnetic field B0 and the transmit radiofrequency (RF) field B1+. The inhomogeneous B fields do not only demand for improved shimming methods, but they furthermore impede the correct determination of the zero order terms, i.e. the local resonance frequency f0 and the RF power to generate the intended local B1+ field. In this work dual echo time B0-map and dual flip angle B1+-map acquisition methods are combined to acquire multi-slice B0- and B1+-maps simultaneously covering the entire heart in a single breath-hold of 18 heart beats. A previously proposed excitation pulse shape dependent slice profile correction is tested and applied to reduce systematic errors of the multi-slice B1+-map. Localized higher order shim correction values including the zero order terms for frequency f0 and RF power can be determined based on the acquired B0- and B1+-maps. This method has been tested in 7 healthy adult human subjects at 3T and improved the B0 field homogeneity (standard deviation) from 60Hz to 35Hz and the average B1+ field from 77% to 100% of the desired B1+ field when compared to more commonly used preparation methods.
cardiac MR; 3 Tesla; localized shimming; localized power preparation; B1-map; B0-map
The susceptibility of blood changes after administration of a paramagnetic contrast agent which shortens T1. Concomitantly the resonance frequency of the blood vessels shifts in a geometry-dependent way. This frequency change may be exploited for incremental contrast generation by applying a frequency selective saturation pre-pulse prior to the imaging sequence. The dual origin of vascular enhancement depending firstly on off-resonance and secondly on T1 lowering was investigated in vitro together with the geometry dependence of the signal at 3T. First results obtained in an in vivo rabbit model are presented.
Magnetic Resonance Angiography; Off-resonance imaging; Blood-pool contrast agent
Cardiovascular magnetic resonance (CMR) imaging has evolved rapidly and is now accepted as a powerful diagnostic tool with significant clinical and research applications. Clinical 3 Tesla (3 T) scanners are increasingly available and offer improved diagnostic capabilities compared to 1.5 T scanners for perfusion, viability, and coronary imaging. Although technical challenges remain for cardiac imaging at higher field strengths such as balanced steady state free precession (bSSFP) cine imaging, the majority of cardiac applications are feasible at 3 T with comparable or superior image quality to that of 1.5 T. This review will focus on the benefits and limitations of 3 T CMR for common clinical applications and examine areas in development for potential clinical use.
3 Tesla; cardiac magnetic resonance.
As the number of MRI phased array coil elements grows, interactions among cables connecting them to the system receiver become increasingly problematic. Fiber optic or wireless links would reduce electromagnetic interference, but their dynamic range (DR) is generally less than that of coaxial cables. Raw MRI signals, however, have a large DR because of the high signal amplitude near the center of k-space. Here, we study DR in MRI in order to determine the compatibility of MRI multicoil imaging with non-coaxial cable signal transmission. Since raw signal data are routinely discarded, we have developed an improved method for estimating the DR of MRI signals from conventional magnitude images. Our results indicate that the DR of typical surface coil signals at 3 T for human subjects is less than 88 dB, even for three-dimensional acquisition protocols. Cardiac and spine coil arrays had a maximum DR of less than 75 dB and head coil arrays less than 88 dB. The DR derived from magnitude images is in good agreement with that measured from raw data. The results suggest that current analog fiber optic links, with a spurious-free DR of 60–70 dB at 500 kHz bandwidth, are not by themselves adequate for transmitting MRI data from volume or array coils with DR ~90 dB. However, combining analog links with signal compression might make non-coaxial cable signal transmission viable.
Dynamic range; Magnetic resonance imaging; MRI; Magnitude image; Fiber optic link; Wireless link; Signal-to-noise ratio