Dmitriy A. Yablonskiy

Water proton MR properties of human blood at 1.5 Tesla: Magnetic susceptibility, T1, T2, T *2, and non‐Lorentzian signal behavior

Accurate knowledge of the magnetic properties of human blood is required for the precise modeling of functional and vascular flow‐related MRI. Herein are reported determinations of the relaxation parameters of blood, employing in vitro samples that are well representative of human blood in situ. The envelope of the blood 1H2O free‐induction decay signal magnitude during the first 100 msec following a spin echo at time TE is well‐ described empirically by an expression of the form, S(t) = So · exp{–R  *2 · (t – TE) – AR* · (t – TE)2}. The relaxation parameters AR* and R  *2 increase as a function of the square of the susceptibility difference between red blood cell and plasma and depend on the spin‐echo time. The Gaussian component, AR*, should be recognized in accurate modeling of MRI phenomena that depend upon the magnetic state of blood. The magnetic susceptibility difference between fully deoxygenated and fully oxygenated red blood cells at 37°C is 0.27 ppm, as determined independently by MR and superconducting quantum interference device (SQUID) measurements. This value agrees well with the 1936 report of Pauling and Coryell (Proc Natl Acad Sci USA 1936;22:210–216), but is substantially larger than that frequently used in MRI literature. Magn Reson Med 45:533–542, 2001.

Quantitative in vivo assessment of lung microstructure at the alveolar level with hyperpolarized 3He diffusion MRI

The study of lung emphysema dates back to the beginning of the 17th century. Nevertheless, a number of important questions remain unanswered because a quantitative localized characterization of emphysema requires knowledge of lung structure at the alveolar level in the intact living lung. This information is not available from traditional imaging modalities and pulmonary function tests. Herein, we report the first in vivo measurements of lung geometrical parameters at the alveolar level obtained with 3He diffusion MRI in healthy human subjects and patients with severe emphysema. We also provide the first experimental data demonstrating that 3He gas diffusivity in the acinus of human lung is highly anisotropic. A theory of anisotropic diffusion is presented. Our results clearly demonstrate substantial differences between healthy and emphysematous lung at the acinar level and may provide new insights into emphysema progression. The technique offers promise as a clinical tool for early diagnosis of emphysema.

MR imaging of diffusion of 3He gas in healthy and diseased lungs

Hyperpolarized 3He gas MRI was used to form maps of the effective diffusivity of gas in human lungs. Images of diffusion as well as spin density are presented from a study of 11 healthy volunteers and 5 patients with severe emphysema. The effective rate of diffusion, De, of the gas is reduced by the alveolar walls; tissue destruction in emphysema is hypothesized to result in larger De. Indeed, the mean value of De in the emphysematous lungs is found here to be about 2.5 times that of healthy lungs, although still smaller than the unrestricted diffusivity of 3He in free air. Histograms of De values across coronal slices are presented. The results are discussed in terms of spatial variations, variations among individuals, healthy and diseased, and variations due to changes in lung volume. Magn Reson Med 44:174–179, 2000.

Quantitative BOLD: Mapping of Human Cerebral Deoxygenated Blood Volume and Oxygen Extraction Fraction: Default State

Since Ogawa et al. (Proc Natl Acad Sci USA 1990;87:9868–9872) made the fundamental discovery of blood oxygenation level‐dependent (BOLD) contrast in MRI, most efforts have been directed toward the study of dynamic BOLD (i.e., temporal changes in the MRI signal during changes in brain activity). However, very little progress has been made in elucidating the nature of BOLD contrast during the resting or baseline state of the brain, which is important for understanding normal human performance because it accounts for most of the enormous energy budget of the brain. It is also crucial for deciphering the consequences of baseline‐state impairment by cerebral vascular diseases. The objective of this study was to develop a BOLD MR‐based method that allows quantitative evaluation of tissue hemodynamic parameters, such as the blood volume, deoxyhemoglobin concentration, and oxygen extraction fraction (OEF). The proposed method, which we have termed quantitative BOLD (qBOLD), is based on an MR signal model that incorporates prior knowledge about brain tissue composition and considers signals from gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), and blood. A 2D gradient‐echo sampling of spin‐echo (GESSE) pulse sequence is used for the acquisition of the MRI signal. The method is applied to estimate the hemodynamic parameters of the normal human brain in the baseline state. Magn Reson Med 57:115–126, 2007.

Biophysical mechanisms of phase contrast in gradient echo MRI

Recently reported contrast in phase images of human and animal brains obtained with gradient-recalled echo MRI holds great promise for the in vivo study of biological tissue structure with substantially improved resolution. Herein we investigate the origins of this contrast and demonstrate that it depends on the tissue “magnetic architecture” at the subcellular and cellular levels. This architecture is mostly determined by the structural arrangements of proteins, lipids, non-heme tissue iron, deoxyhemoglobin, and their magnetic susceptibilities. Such magnetic environment affects/shifts magnetic resonance (MR) frequencies of the water molecules moving/diffusing in the tissue. A theoretical framework allowing quantitative evaluation of the corresponding frequency shifts is developed based on the introduced concept of a generalized Lorentzian approximation. It takes into account both tissue architecture and its orientation with respect to the external magnetic field. Theoretical results quantitatively explain frequency contrast between GM, WM, and CSF previously reported in motor cortex area, including the absence of the contrast between WM and CSF. Comparison of theory and experiment also suggests that in a normal human brain, proteins, lipids, and non-heme iron provide comparable contributions to tissue phase contrast; however, the sign of iron and lipid contributions is opposite to the sign of contribution from proteins. These effects of cellular composition and architecture are important for quantification of tissue microstructure based on MRI phase measurements. Also theory predicts the dependence of the signal phase on the orientation of WM fibers, holding promise as additional information for fiber tracking applications.

Modeling dendrite density from magnetic resonance diffusion measurements.

Diffusion-weighted imaging (DWI) provides a noninvasive tool to probe tissue microstructure. We propose a simplified model of neural cytoarchitecture intended to capture the essential features important for water diffusion as measured by NMR. Two components contribute to the NMR signal in this model: (i) the dendrites and axons, which are modeled as long cylinders with two diffusion coefficients, parallel (D(L)) and perpendicular (D(T)) to the cylindrical axis, and (ii) an isotropic monoexponential diffusion component describing water diffusion within and across all other structures, i.e., in extracellular space and glia cells. The model parameters are estimated from 153 diffusion-weighted images acquired from a formalin-fixed baboon brain. A close correspondence between the data and the signal model is found, with the model parameters consistent with literature values. The model provides an estimate of dendrite density from noninvasive MR diffusion measurements, a parameter likely to be of value for understanding normal as well as abnormal brain development and function.

Hyperpolarized 3He diffusion MRI and histology in pulmonary emphysema.

Diffusion MRI of hyperpolarized 3He shows that the apparent diffusion coefficient (ADC) of 3He gas is highly restricted in the normal lung and becomes nearly unrestricted in severe emphysema. The nature of this restricted diffusion provides information about lung structure; however, no direct comparison with histology in human lungs has been reported. The purpose of this study is to provide information about 3He gas diffusivity in explanted human lungs, and describe the relationship between 3He diffusivity and the surface area to lung volume ratio (SA/V) and mean linear intercept (Lm) measurements—the gold standard for diagnosis of emphysema. Explanted lungs from patients who were undergoing lung transplantation for advanced COPD, and donor lungs that were not used for transplantation were imaged via 3He diffusion MRI. Histological measurements were made on the same specimens after they were frozen in the position of study. There is an inverse correlation between diffusivity and SA/V (and a positive correlation between diffusivity and Lm). An important result is that restricted 3He diffusivity separated normal from emphysematous lung tissue more clearly than the morphometric analyses. This effect may be due to the smaller histologic sampling size compared to the MRI voxel sizes. Magn Reson Med, 2006.

Statistical model for diffusion attenuated MR signal.

A general statistical model that can describe a rather large number of experimental results related to the structure of the diffusion‐attenuated MR signal in biological systems is introduced. The theoretical framework relies on a phenomenological model that introduces a distribution function for tissue apparent diffusion coefficients (ADC). It is shown that at least two parameters—the position of distribution maxima (ADC) and the distribution width (σ)—are needed to describe the MR signal in most regions of a human brain. A substantial distribution width, on the order of 36% of the ADC, was found for practically all brain regions examined. This method of modeling the MR diffusion measurement allows determination of an intrinsic tissue‐specific ADC for a given diffusion time independent of the strength of diffusion sensitizing gradients. The model accounts for the previously found biexponential behavior of the diffusion‐attenuated MR signal in CNS. Magn Reson Med 50:664–669, 2003.

Neurite density from magnetic resonance diffusion measurements at ultrahigh field: Comparison with light microscopy and electron microscopy

Due to its unique sensitivity to tissue microstructure, diffusion-weighted magnetic resonance imaging (MRI) has found many applications in clinical and fundamental science. With few exceptions, a more precise correspondence between physiological or biophysical properties and the obtained diffusion parameters remain uncertain due to lack of specificity. In this work, we address this problem by comparing diffusion parameters of a recently introduced model for water diffusion in brain matter to light microscopy and quantitative electron microscopy. Specifically, we compare diffusion model predictions of neurite density in rats to optical myelin staining intensity and stereological estimation of neurite volume fraction using electron microscopy. We find that the diffusion model describes data better and that its parameters show stronger correlation with optical and electron microscopy, and thus reflect myelinated neurite density better than the more frequently used diffusion tensor imaging (DTI) and cumulant expansion methods. Furthermore, the estimated neurite orientations capture dendritic architecture more faithfully than DTI diffusion ellipsoids.

Quantification of lung microstructure with hyperpolarized 3He diffusion MRI

The structure and integrity of pulmonary acinar airways and their changes in different diseases are of great importance and interest to a broad range of physiologists and clinicians. The introduction of hyperpolarized gases has opened a door to in vivo studies of lungs with MRI. In this study we demonstrate that MRI-based measurements of hyperpolarized (3)He diffusivity in human lungs yield quantitative information on the value and spatial distribution of lung parenchyma surface-to-volume ratio, number of alveoli per unit lung volume, mean linear intercept, and acinar airway radii-parameters that have been used by lung physiologists for decades and are accepted as gold standards for quantifying emphysema. We validated our MRI-based method in six human lung specimens with different levels of emphysema against direct unbiased stereological measurements. We demonstrate for the first time MRI images of these lung microgeometric parameters in healthy lungs and lungs with different levels of emphysema (mild, moderate, and severe). Our data suggest that decreases in lung surface area per volume at the initial stages of emphysema are due to dramatic decreases in the depth of the alveolar sleeves covering the alveolar ducts and sacs, implying dramatic decreases in the lungs gas exchange capacity. Our novel methods are sufficiently sensitive to allow early detection and diagnosis of emphysema, providing an opportunity to improve patient treatment outcomes, and have the potential to provide safe and noninvasive in vivo biomarkers for monitoring drug efficacy in clinical trials.