Biomedical subjects

Dmitriy A Yablonskiy

Publications and source records attributed to Dmitriy A Yablonskiy.

16 recordsLinked to original sources

PubMed2005

Long-range diffusion of hyperpolarized 3He in explanted normal and emphysematous human lungs via magnetization tagging.

Long-range diffusivity of hyperpolarized 3He gas was measured from the decay rate of sinusoidally modulated longitudinal nuclear magnetization in three normal donor and nine severely emphysematous explanted human lungs. This (long-range) diffusivity, which we call Dsec, is measured over seconds and centimeters and is approximately 10 times smaller in healthy lungs (0.022 cm2/s) than the more traditionally measured Dmsec, which is measured over milliseconds and submillimeters. The increased restriction of Dsec reflects the complex, tortuous paths required to navigate long distances through the maze of branching peripheral airways. In emphysematous lungs, Dsec is substantially increased, with some regions showing nearly the unrestricted value of the self-diffusion coefficient (0.88 cm2/s for dilute 3He in air, a 40-fold increase). This suggests the presence of large collateral pathways opened by alveolar destruction that bypass the airways proper. This destruction was confirmed by comparison with histology in seven lungs and by removal of trapped gas via holes in the pleural surface in five lungs.

Emphysema↗

PubMed2005

19F MR imaging of ventilation and diffusion in excised lungs.

Perfluorinated gases, particularly C2F6, are potentially suitable alternatives to hyperpolarized noble gases for pulmonary airspace spin density and diffusion MRI. This work focuses mainly on 19F imaging of C2F6 gas in healthy and emphysematous explanted lungs, avoiding regulatory issues of human in vivo measurements. Three-dimensional gradient echo and spin echo spin density images of human lungs can be made in 10 s with adequate signal-to-noise, demonstrating the feasibility for breathing dynamics to be captured during a succession of short breath holds. As expected, the spin echo images have much smaller susceptibility artifacts than the gradient echo images. 19F and 3He images of the same lungs are compared. The apparent diffusion coefficient (ADC) of C2F6 is sensitive to restrictions imposed by the lung microstructure: the average ADC is measured to be 0.018 cm2/s in healthy lungs versus 0.031 cm2/s in emphysematous lungs at a diffusion time Delta=2.2 ms. The low free diffusivity of pure C2F6 (D0=0.033 cm2/s) places it in a regime where the ADC measurement allows the surface-to-volume ratio to be determined in each voxel, a potentially valuable quantitative characterization of regional lung tissue destruction in emphysema.

Animals↗

PubMed2005

Feasibility of combining MR perfusion, angiography, and 3He ventilation imaging for evaluation of lung function in a porcine model.

RATIONALE AND OBJECTIVE: To assess the feasibility of combining magnetic resonance (MR) perfusion, angiography, and 3He ventilation imaging for the evaluation of lung function in a porcine model. MATERIALS AND METHODS: Fourteen consecutive porcine models with externally delivered pulmonary emboli and/or airway occlusions were examined with MR perfusion, angiography, and 3He ventilation imaging. Ultrafast gradient-echo sequences were used for 3D perfusion and angiographic imaging, in conjunction with the use of contrast-agent injections. 2D multiple-section 3He imaging was performed subsequently via the inhalation of hyperpolarized 3He gas. The diagnostic accuracy of MR angiography for detecting pulmonary emboli was determined by two reviewers. The diagnostic confidence for different combinations of MR techniques was rated on the basis of a 5-point grading scale (5 = definite). RESULTS: The sensitivity, specificity, and accuracy of MR angiography for detecting pulmonary emboli were approximately 85.7%, 90.5%, and 88.1%, respectively. The interobserver agreement was very strong (k = 0.82). There was a clear tendency for confidence to increase when first perfusion and then ventilation imaging were added to the angiographic image (Wilcoxon signed ranks test, P = 0.03). CONCLUSION: The combination of the three methods of MR perfusion, angiography, and 3H ventilation imaging may provide complementary information on abnormal lung anatomy and function.

Administration, Inhalation↗

PubMed2005

3He diffusion MRI of the lung.

RATIONALE AND OBJECTIVES: MR imaging of the restricted diffusion of laser-polarized 3He gas provides unique insights into the changes in lung microstructure in emphysema. RESULTS: We discuss measurements of ventilation (spin density), mean diffusivity, and the anisotropy of diffusion, which yields the mean acinar airway radius. In addition, the use of spatially modulated longitudinal magnetization allows diffusion to be measured over longer distances and times, with sensitivity to collateral ventilation paths. Early results are also presented for spin density and diffusivity maps made with a perfluorinated inert gas, C3F8. METHODS: Techniques for purging and imaging excised lungs are discussed.

Diffusion Magnetic Resonance Imaging↗

PubMed2005

Image artifacts in very low magnetic field MRI: the role of concomitant gradients.

While MRI at very low magnetic fields has certain potential advantages, it may also face problems that are not typical for MRI at conventional and high field (0.1-10T). Major differences arise due to the presence of concomitant components of inhomogeneous magnetic field (gradients) that are transverse to the major B(z) field, B(0). These concomitant transverse field components are inevitably generated by the same gradient coils that generate desired B(z) imaging gradients as routinely used in MRI for spatial encoding. In the hypothetical case (linear spatial variation of B(z) field amplitude due to the imaging gradients, no concomitant transverse field components, no B(0) and B(1) field inhomogeneities, etc.), Fourier transform MRI preserves the shape of the real object being examined. It is demonstrated herein that unavoidable concomitant transverse field gradients, G, result in an image deformation of the object's actual shape by bending straight lines and planes with a characteristic curvature radius R(c)=B(0)/G. For imaging gradients on the order of 10 mT/m and B(0) of 1T, the radius R(c) is about 100 m and image distortions are generally negligible. However, for B(0) of 1 mT, R(c) is 10 cm, which is less than a typical FOV in human studies. This manuscript derives expressions describing geometrical relationships between the imaged object and the obtained MR data. In addition to geometrical distortions, image intensity will be modulated in a complex, spatially dependent manner. Hence, if unaccounted for, corresponding image distortions-geometry and intensity-will create substantial difficulties in very low field image interpretation.

Artifacts↗

PubMed2004

Thermal contribution of compact bone to intervening tissue-like media exposed to planar ultrasound.

The presence of bone in the ultrasound beam path raises concerns, both in diagnostic and therapeutic applications, because significant temperature elevations may be induced at nearby soft tissue-bone interfaces due the facts that ultrasound is (i) highly absorbed in bone and (ii) reflected at soft tissue-bone interfaces in various degrees depending on angle of incidence. Consequently, in ultrasonic thermal therapy, the presence of bone in the ultrasound beam path is considered a major disadvantage and it is usually avoided. However, based on clinical experience and previous theoretical studies, we hypothesized that the presence of bone in superficial unfocused ultrasound hyperthermia can actually be exploited to induce more uniform and enhanced (with respect to the no-bone situation) temperature distributions in superficial target volumes. In particular, we hypothesize that the presence of underlying bone in superficial target volume enhances temperature elevation not only by additional direct power deposition from acoustic reflection, but also from thermal diffusion from the underlying bone. Here we report laboratory results that corroborate previous computational studies and strengthen the above-stated hypothesis. Three different temperature measurement techniques, namely, thermometric (using fibre-optic temperature probes), thermographic (using an infrared camera) and magnetic resonance imaging (using proton resonance frequency shifts), were used in high-power short-exposure, and in low-power extended-exposure, experiments using a 19 mm diameter planar transducer operating at 1.0 and 3.3 MHz (frequencies of clinical relevance). The measurements were performed on three technique-specific phantoms (with and without bone inclusions) and experimental set-ups that resembled possible superficial ultrasound hyperthermia clinical situations. Results from all three techniques were in general agreement and clearly showed that significantly higher heating rates (greater than fourfold) were induced in soft tissue-like phantom materials adjacent (within approximately 5 mm) to a bovine bone as compared to similar experiments without bone inclusions. For low-power long-exposure experiments, where thermal conduction effects are significant, the thermal impact of bone reached at distances > 10 mm from the bone surface (upstream of the bone). Therefore, we hypothesize that underlying bone exposed to planar ultrasound hyperthermia creates a high-temperature thermal boundary at depth that compensates for beam attenuation, thus producing more uniform temperature distribution in the intervening tissue layers. With appropriate technology, this finding may lead to improved thermal doses in superficial treatment sites such as the chest wall and the head/neck.

Animals↗

PubMed2004

Magnetization tagging decay to measure long-range (3)He diffusion in healthy and emphysematous canine lungs.

Spatial modulation (tagging) of the longitudinal magnetization allows diffusive displacements to be measured over times approximately as long as T(1) and over correspondingly long distances. Magnetization tagging is used here with hyperpolarized (3)He gas in canine lungs with unilateral elastase-induced emphysema. A new scheme for analyzing images subsequent to tagging determines the spatially-resolved fractional modulation and its decay rate, using a sliding window. The diffusivity so determined over seconds and centimeter lengths, D(sec), is smaller in all cases than the diffusivity measured over milliseconds and hundreds of microns, D(msec) (in healthy lungs, this ratio is about 0.1). While D(msec) is sensitive to lung microstructure on the alveolar level, D(sec) reflects airway connectivity and provides new information on lung structure. The results show substantial increases in D(sec) in the lungs of four dogs with clear evidence of emphysema. For these dogs, the fractional increase in long-range diffusivity D(sec) in the emphysematous lungs was greater than that in short-range diffusivity D(msec).

Animals↗

PubMed2004

On the nature of the NAA diffusion attenuated MR signal in the central nervous system.

In the brain, on a macroscopic scale, diffusion of the intraneuronal constituent N-acetyl-L-aspartate (NAA) appears to be isotropic. In contrast, on a microscopic scale, NAA diffusion is likely highly anisotropic, with displacements perpendicular to neuronal fibers being markedly hindered, and parallel displacements less so. In this report we first substantiate that local anisotropy influences NAA diffusion in vivo by observing differing diffusivities parallel and perpendicular to human corpus callosum axonal fibers. We then extend our measurements to large voxels within rat brains. As expected, the macroscopic apparent diffusion coefficient (ADC) of NAA is practically isotropic due to averaging of the numerous and diverse fiber orientations. We demonstrate that the substantially non-monoexponential diffusion-mediated MR signal decay vs. b value can be quantitatively explained by a theoretical model of NAA confined to an ensemble of differently oriented neuronal fibers. On the microscopic scale, NAA diffusion is found to be strongly anisotropic, with displacements occurring almost exclusively parallel to the local fiber axis. This parallel diffusivity, ADCparallel, is 0.36 +/- 0.01 microm2/ms, and ADCperpendicular is essentially zero. From ADCparallel the apparent viscosity of the neuron cytoplasm is estimated to be twice as large as that of a temperature-matched dilute aqueous solution.

Animals↗

PubMed2004

Gaussian approximation in the theory of MR signal formation in the presence of structure-specific magnetic field inhomogeneities. Effects of impermeable susceptibility inclusions.

A detailed theoretical description of the signal formation in the presence of mesoscopic structure-specific magnetic field inhomogeneities is presented in the framework of the Gaussian phase distribution approximation for two geometrical models of the field inhomogeneity sources--impermeable spheres and infinitely long cylinders. Analytical expressions for free induction decay (FID) and spin echo (SE) signal attenuation functions Gamma(t) approximately -1nS(t) are obtained and comparison with the case of unrestricted diffusion (susceptibility inclusions with freely permeable surfaces) is provided. For short times, the leading term in the FID signal attenuation function is proportional to t2 similar to the case of unrestricted diffusion; the next term behaves as t3 as compared to t 5/2 for the "permeable" case. For the SE signal, the leading term is proportional to t3 as compared to t 5/2 for unrestricted diffusion. It is shown that the t3 approximation can be used for an adequate description of the SE signal only for extremely short times compared to a characteristic diffusion time. In the long-time limit, the attenuation function in the impermeable and permeable sphere model contains not only terms linear in time, but also important terms proportional to t 1/2. In the cylindrical geometry, the leading term in the long-time expansion of the attenuation function is proportional to t 1n t for both the permeable and impermeable models. Application to description of MR in biological tissues signal in the presence of blood vessel networks and contrast agents is discussed. The validity criterion of the Gaussian approximation is also proposed.

Algorithms↗

PubMed2003

Albumin-binding MR blood pool agents as MRI contrast agents in an intracranial mouse glioma model.

Intravenous MRI contrast agents are commonly used to improve the detection of intracranial tumors and other central nervous system (CNS) lesions for diagnosis and treatment planning. Two small-molecule, albumin-binding blood pool contrast agents (MP-2269 and MS-325) of potential clinical significance were evaluated at 1.5 Tesla in a mouse glioma model and compared with an extracellular contrast agent (OptiMARK). Tumor image contrast was significantly enhanced and long-lived following administration of 30 micromole/kg of the blood pool agents: specifically, contrast enhancement peaked slowly at 25-30 min following administration, remained constant for >3 hr, and returned to baseline within 20 hr. Comparable but "transient" enhancement was achieved using 100 micromole/kg OptiMARK: specifically, contrast enhancement peaked rapidly at 2-5 min following administration and then declined over 40 min. The blood pool contrast agents demonstrated an approximately threefold increased dose-effectiveness and a lengthened window of tumor contrast enhancement in comparison to commonly available extracellular contrast agents. This demonstrates the potential of alternative contrast-enhanced (CE) MRI examination protocols for tumor detection.

Albumins↗

PubMed2003

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 (sigma)--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.

Brain↗

PubMed2003

Gaussian approximation in the theory of MR signal formation in the presence of structure-specific magnetic field inhomogeneities.

A detailed theoretical analysis of the free induction decay (FID) and spin echo (SE) MR signal formation in the presence of mesoscopic structure-specific magnetic field inhomogeneities is developed in the framework of the Gaussian phase distribution approximation. The theory takes into account diffusion of nuclear spins in inhomogeneous magnetic fields created by arbitrarily shaped magnetized objects with permeable boundaries. In the short-time limit the FID signal decays quadratically with time and depends on the objects' geometry only through the volume fraction, whereas the SE signal decays as 5/2 power of time with the coefficient depending on both the volume fraction of the magnetized objects and their surface-to-volume ratio. In the motional narrowing regime, the FID and SE signals for objects of finite size decay mono-exponentially; a simple general expression is obtained for the relaxation rate constant deltaR2. In the case of infinitely long cylinders in the motional narrowing regime the theory predicts non-exponential signal decay lnS approximately -tlnt in accordance with previous results. For specific geometries of the objects (spheres and infinitely long cylinders) exact analytical expressions for the FID and SE signals are given. The theory can be applied, for instance, to biological systems where mesoscopic magnetic field inhomogeneities are induced by deoxygenated red blood cells, capillary network, contrast agents, etc.

Anisotropy↗

PubMed2002

Fatty liver in familial hypobetalipoproteinemia: triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis.

Familial hypobetalipoproteinemia (FHBL) subjects may develop fatty liver. Liver fat was assessed in 21 FHBL with six different apolipoprotein B (apoB) truncations (apoB-4 to apoB-89) and 14 controls by magnetic resonance spectroscopy (MRS). Liver fat percentages were 16.7 +/- 11.5 and 3.3 +/- 2.9 (mean +/- SD) (P = 0.001). Liver fat percentage was positively correlated with body mass index, waist circumference, and areas under the insulin curves of 2 h glucose tolerance tests, suggesting that obesity may affect the severity of liver fat accumulation in both groups. Despite 5-fold differences in liver fat percentage, mean values for obesity and insulin indexes were similar. Thus, for similar degrees of obesity, FHBL subjects have more hepatic fat. VLDL-triglyceride (TG)-fatty acids arise from plasma and nonplasma sources (liver and splanchnic tissues). To assess the relative contributions of each, [2H2]palmitate was infused over 12 h in 13 FHBL subjects and 11 controls. Isotopic enrichment of plasma free palmitate and VLDL-TG-palmitate was determined by mass spectrometry. Non-plasma sources contributed 51 +/- 15% in FHBL and 37 +/- 13% in controls (P = 0.02). Correlations of liver fat percentage and percent VLDL-TG-palmitate from liver were r = 0.89 (P = 0.0001) for FHBL subjects and r = 0.69 (P = 0.01) for controls. Thus, apoB truncation-producing mutations result in fatty liver and in altered assembly of VLDL-TG.

Adult↗

PubMed2002

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.

Diffusion↗

PubMed2002

Combined MR proton lung perfusion/angiography and helium ventilation: potential for detecting pulmonary emboli and ventilation defects.

Three-dimensional (3D) perfusion imaging allows the assessment of pulmonary blood flow in parenchyma and main pulmonary arteries simultaneously. MRI using laser-polarized (3)He gas clearly shows the ventilation distribution with high signal-to-noise ratio (SNR). In this report, the feasibility of combined lung MR angiography, perfusion, and ventilation imaging is demonstrated in a porcine model. Ultrafast gradient-echo sequences have been used for 3D perfusion and angiographic imaging, in conjunction with the use of contrast agent injections. 2D multiple-section (3)He imaging was performed subsequently by inhalation of 450 ml of hyperpolarized (3)He gas. The MR techniques were examined in a series of porcine models with externally delivered pulmonary emboli and/or airway occlusions. With emboli, perfusion deficits without ventilation defects were observed; airway occlusion resulted in matched deficits in perfusion and ventilation. High-resolution MR angiography can unambiguously reveal the location and size of the blood emboli. The combination of the three imaging methods may provide complementary information on abnormal lung anatomy and function.

Airway Obstruction↗

PubMed2002

Effects of restricted diffusion on MR signal formation.

Numerous functional MRI (fMRI) and diffusion MR studies have recently boosted interest in the theory of MR signal formation in biological systems in the presence of mesoscopic magnetic field in homogeneities. Herein we report an exact solution to the problem of free induction decay (FID) and spin echo (SE) signal formation in the presence of a constant field gradient in three models of one-, two-, and three-dimensional restricted diffusion. We demonstrate the transition with increasing diffusion coefficient from the oscillating FID signal behavior in the static dephasing regime to a monotonic exponential behavior in the motional narrowing regime. Quantitative criteria are presented for applicability of the Gaussian approximation for the description of the MR signal. The spatial distribution of signal density and the edge enhancement effect are analyzed. We also demonstrate that the presence of restrictive barriers in a one-compartment model can lead to a quasi-two-compartment behavior of the MR signal. This result suggests a simple rationale for the experimental findings of biexponential echo attenuation curves in MR diffusion experiments with tissue systems.

Diffusion↗