Biomedical subjects
Publications and source records attributed to D Le Bihan.
MR measurements based on motion encoding gradients, such as intravoxel incoherent motion imaging, could provide, in principle, information on flowing blood volume and blood velocity. This note shows that, in addition, the knowledge of the capillary network organization may provide a link between these measurements and those obtained by conventional and MR perfusion techniques based on tracer uptake by tissues.
Perfusion magnetic resonance imaging (MRI) offers relative safety (no ionizing radiation), high spatial/temporal resolution, multi-orientation imaging capability, and relative low cost when compared with sophisticated techniques, such as positron emission tomography (PET). Several methods have been recently proposed to image perfusion. Some techniques mimic conventional nuclear medicine principles, but use radioactively inert tracers. Other approaches directly use blood as an endogenous natural tracer. Such methods are totally noninvasive, and offer original insights, for instance by monitoring variations in blood oxygenation in human brain cortex during activation tasks. These methods are presented and compared. Emphasis is given on advantages and drawbacks, and potential clinical applications.
Water self-diffusion, a recently discovered source of contrast on MR images, has already shown promise for some clinical applications. Most studies have been of the brain, essentially for technical reasons. Diffusion is useful in distinguishing the different components of brain tumors (cystic regions, edema, necrosis) from the tumor core itself. Recent studies have shown that diffusion is anisotropic in brain white matter (i.e., dependent on the fiber tract's orientation in space), offering new insights into myelin disorders. Diffusion is also dramatically altered in the minutes following ischemic injury in the cat brain, which may have tremendous impact for the diagnosis and management of hyperacute stroke. With ultrafast acquisition schemes, diffusion imaging has also been used outside the CNS, for instance, in the eye and kidney. Future applications include diffusion-localized spectroscopy and temperature imaging. This article reviews recent progress in this field and suggests potential applications.
The purpose of this paper is to review the basic principles of diffusion measurement with spin echoes. These principles can be combined with those of MR imaging to generate maps of diffusion coefficients. Diffusion imaging can be extended to imaging of other intravoxel incoherent motions (IVIM), such as blood microcirculation. Some of the technical problems encountered when implementing IVIM imaging are presented.
Use of the Stejskal-Tanner sequence for performing diffusion images in the human brain tends to be complicated by the presence of artifacts caused by voluntary or involuntary, sometimes pulsatile, motion. We describe the implementation of the technique of echo-planar diffusion imaging, which avoids these artifacts and allows reproducible quantitative values of the diffusion coefficient to be measured in vivo. The effects of perfusion are easily visible in a phantom containing a gel. The results for human brain show a significant "perfusion fraction" in grey matter, consistent with an extracellular, possibly microvascular, volume of about 10%.
Efficacy and safety considerations for cancer therapy with hyperthermia require accurate temperature measurements throughout the heated volume. We report the use of molecular diffusion, whose temperature dependence is well known. A dedicated hyperthermia applicator was built, combining a MRI gradient coil and a rf coil. Diffusion and derived temperature images were obtained with a 1 x 2 mm pixel size on a polyacrylamide gel phantom using a clinical 1.5-T whole body MRI system. Temperatures determined from these images using 1 cm2 regions of interest were found to be within 0.2 degrees C of those recorded from the thermocouples and fiber-optic probes placed inside the gel.
When deoxygenated, blood behaves as an effective susceptibility contrast agent. Changes in brain oxygenation can be monitored using gradient-echo echo-planar imaging. With this technique, difference images also demonstrate that blood oxygenation is increased during periods of recovery from respiratory challenge.
This review summarizes the work performed during the last 40 years in the field of diffusion measurement by nuclear magnetic resonance (NMR), with emphasis on biomedical diffusion imaging. Measuring molecular displacements in biological tissues in vivo has an enormous potential, but remains technically challenging. After a review of the nature of the diffusion process, the basic principles of diffusion measurements with NMR are introduced, followed by a presentation of various diffusion imaging methods. The paper covers many previously resolved theoretical and technical issues and new problems that are more specific to clinical diffusion imaging, such as the calculation of diffusion effects in the presence of multiple magnetic field gradient pulses, the elimination of motion artifacts, and the meaning of anisotropic or restricted diffusion in relation to tissue microdynamics and microstructure. The concept of diffusion imaging is then extended to blood microcirculation imaging. Finally, the current and potential clinical applications of these techniques are described.
Magnetic resonance imaging (MRI) is a well-established diagnostic tool that provides detailed information about macroscopic structure and anatomy. Recent advances in MRI allow the noninvasive spatial evaluation of various biophysical and biochemical processes in living systems. Specifically, the motion of water can be measured in processes such as vascular flow, capillary flow, diffusion, and exchange. In addition, the concentrations of various metabolites can be determined for the assessment of regional regulation of metabolism. Examples are given that demonstrate the use of functional MRI for clinical and research purposes. This development adds a new dimension to the application of magnetic resonance to medicine and physiology.
Apparent diffusion coefficients (Da) of individual metabolites can be studied in vivo by diffusion NMR spectroscopy using an echo sequence sensitized to molecular motion. The methods are based on the echo attenuation due to phase dispersion resulting from incoherent displacement during the diffusion time. As the displacement of metabolites by diffusion in vivo can be affected by compartment size, temperature, adsorption processes, etc., the presented methods are potentially useful in studying such phenomena in vivo. Here, the methods are applied to phosphocreatine in the rat quadriceps muscle. It is demonstrated that the displacement of phosphocreatine resembles free diffusion for short diffusion times but becomes limited as a result of boundaries due to compartmentation for longer diffusion times. The limit of the displacement indicates an apparent average size of 44 microns of the compartment in the direction of the diffusion gradient. As the gradient was applied approximately parallel (angle less than 25 degrees) to the muscle fiber, this result indicates that phosphocreatine moves freely in the cytosol but is limited by the boundaries of the muscle cells. Error analyses are performed with regard to motion artifacts and gradient performance. The methods were tested extensively for distilled water and free metabolites.
Recent developments have shown that diffusion and blood microcirculation (perfusion) could be imaged and measured noninvasively by MRI. The purpose of this presentation is to overview the different approaches that use B0 field gradients to monitor diffusion/perfusion. The principles of these different methods are discussed together with their limitations and their potential applications.
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The recently established single-shot technique of echo-planar imaging of intravoxel incoherent motion (IVIM) for determining and imaging the variations of microscopic motions of water has been applied to studies of water perfusion in phantoms and to in vivo studies of diffusion and perfusion in cat and human brains. The phantom results demonstrate that perfusion levels comparable with those found in vivo have easily observable and reproducible effects on signal amplitude that are consistent with previous IVIM theory. Reliable measurements of the diffusion coefficient in various types of brain tissue have been obtained. The results for white matter are consistent with the existence of anisotropic diffusion in oriented bundles of myelinated nerve fibers. The results for gray matter can be fitted to the IVIM theory and suggest a value of up to 14% for the fraction of the signal contributed by randomly perfusing fluid in normal cerebral cortex.
A theoretical analysis of the effects of diffusion and perfusion in steady-state free precession (SSFP) imaging sequences sensitized to intravoxel incoherent motions by magnetic field gradients is presented and supported by phantom studies. The capability of such sequences to image diffusion and perfusion quickly was recently demonstrated. The possible residual effects of T1 and T2 in diffusion measurements are evaluated, as are the effects of the sequence design and the acquisition parameters (repetition time, flip angle, gradient pulses). It is shown theoretically and confirmed by experiments on phantoms that diffusion coefficients can be directly measured from SSFP images when large enough diffusion gradient pulses are used.
Efficacy and safety considerations for hyperthermia (HT) cancer therapy require accurate temperature measurements throughout the heated volume. Noninvasive thermometry methods have been proposed, including magnetic resonance (MR) imaging based on the temperature dependence of the relaxation time T1. However, the temperature accuracy achieved to date with T1 measurements does not fulfill the HT requirements (1 degree C/cm). The authors propose to use molecular diffusion, for which temperature dependence is well known. Molecular diffusion is more sensitive than T1 and can be determined with high accuracy with MR imaging. Diffusion and derived temperature images were obtained with a 2 X 2-mm pixel size in a polyacrylamide gel phantom heated inside the head coil of a clinical 0.5-T whole-body MR imaging system by means of a modified clinical HT device made compatible with the system. Temperatures determined from these images with 0.8-cm2 regions of interest were found to be within 0.5 degrees C of those recorded with thermocouples placed inside the gel. The utility of this method in clinical hyperthermia is enhanced by its potential to also help monitor blood perfusion.
IVIM MR imaging is a method which generates images of diffusion and perfusion in vivo. Until now, intravoxel incoherent motion (IVIM) images have been obtained using spin-echo sequences with extragradient pulses, resulting in long acquisition times (typically 2 x 8 min 32 s). A new method is proposed here, using steady-state free precession (SSFP), which allows IVIM images to be obtained in a couple of minutes. Phantom studies showed that the sensitivity of SSFP to IVIMs is much greater than that of spin echoes. In vivo images are shown.
Intravoxel incoherent motion (IVIM) imaging is a method the authors developed to visualize microscopic motions of water. In biologic tissues, these motions include molecular diffusion and microcirculation of blood in the capillary network. IVIM images are quantified by an apparent diffusion coefficient (ADC), which integrates the effects of both diffusion and perfusion. The aim of this work was to demonstrate how much perfusion contributes to the ADC and to present a method for obtaining separate images of diffusion and perfusion. Images were obtained at 0.5 T with high-resolution multisection sequences and without the use of contrast material. Results in a phantom made of resin microspheres demonstrated the ability of the method to separately evaluate diffusion and perfusion. The method was then applied in patients with brain and bone tumors and brain ischemia. Clinical results showed significant promise of the method for tissue characterization by perfusion patterns and for functional studies in the evaluation of the microcirculation in physiologic and pathologic conditions, as, for instance, in brain ischemia.
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