Recently, several implementations of arterial spin labeling (ASL) techniques have been developed for producing MRI images sensitive to local tissue perfusion. For quantitation of perfusion, both pulsed and continuous labeling methods potentially suffer from a number of systematic errors. In this study, a general kinetic model for the ASL signal is described that can be used to assess these errors. With appropriate assumptions, the general model reduces to models that have been used previously to analyze ASL data, but the general model also provides a way to analyze the errors that result if these assumptions are not accurate. The model was used for an initial assessment of systematic errors due to the effects of variable transit delays from the tagging band to the imaging voxel, the effects of capillary/tissue exchange of water on the relaxation of the tag, and the effects of incomplete water extraction. In preliminary experiments with a human subject, the model provided a good description of pulsed ASL data during a simple sensorimotor activation task.

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A general kinetic model for quantitative perfusion imaging with arterial spin labeling

Within the last several years, the field of terahertz science and technology has changed dramatically. Many new advances in the technology for generation, manipulation, and detection of terahertz radiation have revolutionized the field. Much of this interest has been inspired by the promise of valuable new applications for terahertz imaging and sensing. Among a long list of proposed uses, one finds compelling needs such as security screening and quality control, as well as whimsical notions such as counting the almonds in a bar of chocolate. This list has grown in parallel with the development of new technologies and new paradigms for imaging and sensing. Many of these proposed applications exploit the unique capabilities of terahertz radiation to penetrate common packaging materials and provide spectroscopic information about the materials within. Several of the techniques used for terahertz imaging have been borrowed from other, more well established fields such as x-ray computed tomography and synthetic aperture radar. Others have been developed exclusively for the terahertz field, and have no analogies in other portions of the spectrum. This review provides a comprehensive description of the various techniques which have been employed for terahertz image formation, as well as discussing numerous examples which illustrate the many exciting potential uses for these emerging technologies.

https://iopscience.iop.org/article/10.1088/0034-4885/70/8/R02/pdf

Imaging with terahertz radiation

An important factor in the transition from an open to a closed circulatory system was a change in vessel wall structure and composition that enabled the large arteries to store and release energy during the cardiac cycle. The component of the arterial wall in vertebrates that accounts for these properties is the elastic fiber network organized by medial smooth muscle. Beginning with the onset of pulsatile blood flow in the developing aorta, smooth muscle cells in the vessel wall produce a complex extracellular matrix (ECM) that will ultimately define the mechanical properties that are critical for proper function of the adult vascular system. This review discusses the structural ECM proteins in the vertebrate aortic wall and will explore how the choice of ECM components has changed through evolution as the cardiovascular system became more advanced and pulse pressure increased. By correlating vessel mechanics with physiological blood pressure across animal species and in mice with altered vessel compliance, we show that cardiac and vascular development are physiologically coupled, and we provide evidence for a universal elastic modulus that controls the parameters of ECM deposition in vessel wall development. We also discuss mechanical models that can be used to design better tissue-engineered vessels and to test the efficacy of clinical treatments.

/pdf/vascular-extracellular-matrix-and-arterial-mechanics-5bnvmr10by.pdf

Vascular Extracellular Matrix and Arterial Mechanics

Stimulation of cardiac β1-adrenergic receptors is the main mechanism that increases heart rate and contractility. Consequently, several pharmacological and gene transfer strategies for the prevention of heart failure aim at improving the function of the cardiac β-adrenergic receptor system, whereas current clinical treatment favors a reduction of cardiac stimulation. To address this controversy, we have generated mice with heart-specific overexpression of β1-adrenergic receptors. Their cardiac function was investigated in organ bath experiments as well as in vivo by cardiac catheterization and by time-resolved NMR imaging. The transgenic mice had increased cardiac contractility at a young age but also developed marked myocyte hypertrophy (3.5-fold increase in myocyte area). This increase was followed by progressive heart failure with functional and histological deficits typical for humans with heart failure. Contractility was reduced by ≈50% in 35-week-old mice, and ejection fraction was reduced down to a minimum of ≈20%. We conclude that overexpression of β1-adrenergic receptors in the heart may lead to a short-lived improvement of cardiac function, but that increased β1-adrenergic receptor signalling is ultimately detrimental.

https://www.pnas.org/content/pnas/96/12/7059.full.pdf

Progressive hypertrophy and heart failure in beta1-adrenergic receptor transgenic mice.

In vivo fluorescence imaging in the second near-infrared window (1.0-1.7 μm) can afford deep tissue penetration and high spatial resolution, owing to the reduced scattering of long-wavelength photons. Here we synthesize a series of low-bandgap donor/acceptor copolymers with tunable emission wavelengths of 1,050-1,350 nm in this window. Non-covalent functionalization with phospholipid-polyethylene glycol results in water-soluble and biocompatible polymeric nanoparticles, allowing for live cell molecular imaging at >1,000 nm with polymer fluorophores for the first time. Importantly, the high quantum yield of the polymer allows for in vivo, deep-tissue and ultrafast imaging of mouse arterial blood flow with an unprecedented frame rate of >25 frames per second. The high time-resolution results in spatially and time resolved imaging of the blood flow pattern in cardiogram waveform over a single cardiac cycle (~200 ms) of a mouse, which has not been observed with fluorescence imaging in this window before.

/pdf/ultrafast-fluorescence-imaging-in-vivo-with-conjugated-243zf0wrxp.pdf

Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window

The purpose of this work was to develop high-resolution cardiac magnetic resonance imaging techniques for the in vivo mouse model for quantification of myocardial function and mass. Eight male mice were investigated on a 7-Tesla MRI scanner. High-quality images in multiple short axis slices (in-plane resolution 117 microm2, slice thickness 1 mm) were acquired with an ECG-gated cine sequence. Left ventricular end-diastolic and end-systolic volumes and mass were calculated from segmented slice volumes. There was precise agreement of left ventricular mass determined ex vivo and by MRI. Intraobserver (5%) and interobserver (5%) variability of in vivo MR measurements were low.

Magnetic resonance microimaging for noninvasive quantification of myocardial function and mass in the mouse.

Cardiovascular transgenic mouse models with an early phenotype or even premature death require noninvasive imaging methods that allow for accurate visualization of cardiac morphology and function. Thus the purpose of our study was to assess the feasibility of magnetic resonance imaging (MRI) to characterize cardiac function and mass in newborn, juvenile, and adult mice. Forty-five C57bl/6 mice from seven age groups (3 days to 4 mo after birth) were studied by MRI under isoflurane anesthesia. Electrocardiogram-gated cine MRI was performed with an in-plane resolution of (78-117 microm)(2). Temporal resolution per cine frame was 8.6 ms. MRI revealed cardiac anatomy in mice from all age groups with high temporal and spatial resolution. There was close correlation between MRI- and autopsy-determined left ventricular (LV) mass (r = 0.95, SE of estimate = 9.5 mg). The increase of LV mass (range 9.6-101.3 mg), cardiac output (range 1.1-14.3 ml/min), and stroke volume (range 3. 2-40.2 microl) with age could be quantified by MRI measurements. Ejection fraction and cardiac index did not change with aging. However, LV mass index decreased with increasing age (P < 0.01). High-resolution MRI allows for accurate in vivo assessment of cardiac function in neonatal, juvenile, and adult mice. This method should be useful when applied in transgenic mouse models.

Developmental changes of cardiac function and mass assessed with MRI in neonatal, juvenile, and adult mice.

— The aim of this study was to assess the capability of MRI to characterize systolic and diastolic function in normal and chronically failing mouse hearts in vivo at rest and during inotropic stimulation. Applying an ECG-gated FLASH-cine sequence, MRI at 7 T was performed at rest and after administration of 1.5 μg/g IP dobutamine. There was a significant increase of heart rate, cardiac output, and ejection fraction and significant decrease of end-diastolic and end-systolic left ventricular (LV) volumes ( P <0.01 each) in normal mice during inotropic stimulation. In mice with heart failure due to chronic myocardial infarction (MI), MRI at rest revealed gross LV dilatation. There was a significant decrease of LV ejection fraction in infarcted mice (29%) versus sham mice (58%). Mice with MI showed a significantly reduced maximum LV ejection rate ( P <0.001) and LV filling rate ( P <0.01) and no increase of LV dynamics during dobutamine action, indicating loss of contractile and relaxation reserve. In 4-month-old transgenic mice with cardiospecific overexpression of the β1-adrenergic receptor, which at this early stage do not show abnormalities of resting cardiac function, LV filling rate failed to increase after dobutamine stress (transgenic, 0.19±0.03 μL/ms; wild type, 0.36±0.01 μL/ms; P <0.01). Thus, MRI unmasked diastolic dysfunction during dobutamine stress. Dobutamine-stress MRI allows noninvasive assessment of systolic and diastolic components of heart failure. This study shows that MRI can demonstrate loss of inotropic and lusitropic response in mice with MI and can unmask diastolic dysfunction as an early sign of cardiac dysfunction in a transgenic mouse model of heart failure.

Dobutamine-Stress Magnetic Resonance Microimaging in Mice: Acute Changes of Cardiac Geometry and Function in Normal and Failing Murine Hearts

Measurement of myocardial perfusion is important for the functional assessment of heart in vivo. Our approach is based on the modification of the longitudinal relaxation time T1 induced by magnetic spin labeling of endogenous water protons. Labeling is performed by selectively inverting the magnetization within the detection slice, and longitudinal relaxation is measured using a fast gradient echo MRI technique. As a result of blood flow, nonexcited spins enter the detection slice, which leads to an acceleration of the relaxation rate. Incorporating this phenomenon in a mathematical model that describes tissue as two compartments yields a simple expression that allows the quantification of perfusion from a slice-selective and a global inversion recovery experiment. This model takes into account the difference between T1 in blood and T1 in tissue. Our purpose was to evaluate the feasibility and reproducibility of this technique to map quantitatively myocardial perfusion in vivo in rats. Quantitative maps of myocardial blood flow were obtained from nine rats, and the reproducibility of the technique was evaluated by repeating the whole perfusion experiment four times. Evaluation of regions of interest within the myocardium yielded a mean perfusion value of 3.6 ± .5 ml min−1 g-1 over all animals, which is in good agreement with previously reported literature values.

In vivo quantitative mapping of cardiac perfusion in rats using a noninvasive MR spin-labeling method.

The NMR probehead is a key element of the receiving chain of an NMR spectrometer. To optimize the signal-to-noise ratio the probehead must be adapted for the specific application. This article describes the basic physics and characteristics of NMR probeheads for in vivo applications in small animals and plants as well as quality control procedures on the workbench and in the NMR spectrometer. Various probeheads including volume coils, surface coils, double tuned coils, and microscopy coils are presented and illustrated by results of specific in vivo applications. © 2000 John Wiley & Sons, Inc. Concepts Magn Reson 12: 361–388, 2000

Eberhard Rommel

Papers

Magnetic resonance microimaging for noninvasive quantification of myocardial function and mass in the mouse.

Developmental changes of cardiac function and mass assessed with MRI in neonatal, juvenile, and adult mice.

Dobutamine-Stress Magnetic Resonance Microimaging in Mice: Acute Changes of Cardiac Geometry and Function in Normal and Failing Murine Hearts

In vivo quantitative mapping of cardiac perfusion in rats using a noninvasive MR spin-labeling method.

NMR probeheads for In Vivo applications