Detection of microscopic anisotropy in gray matter and in a novel tissue phantom using double Pulsed Gradient Spin Echo MR

A double Pulsed Gradient Spin Echo (d-PGSE) MR experiment was used to measure and assess the degree of local diffusion anisotropy in brain gray matter, and in a novel "gray matter" phantom that consists of randomly oriented tubes filled with water. In both samples, isotropic diffusion was observed at a macroscopic scale while anisotropic diffusion was observed at a microscopic scale, however, the nature of the resulting echo attenuation profiles were qualitatively different. Gray matter, which contains multiple cell types and fibers, exhibits a more complicated echo attenuation profile than the phantom. Since microscopic anisotropy was observed in both samples in the low q regime comparable to that achievable in clinical scanner, it may offer a new potential contrast mechanism for characterizing gray matter microstructure in medical and biological applications.     

Probing short length scales with restricted diffusion in a static gradient using the CPMG sequence

We experimentally verify a new method of extracting the surface-to-volume ratio (S/V) of porous media with diffusion NMR. In contrast to the widely used pulsed field gradient (PFG) technique, which employs the stimulated echo coherence pathway, we use here the direct Carr-Purcell-Meiboom-Gill (CPMG) path. Even for high echoes, which exhibit ample attenuation due to diffusion in the field gradient, the relevant ruler length for the direct pathway is fixed by the diffusion length during a single inter-pulse spacing. The direct path, therefore, is well suited for probing shorter length scales than is possible with the conventional approach. In our experiments in a low-field static-gradient system, the direct CPMG pathway was found to be sensitive to structure an order of magnitude smaller than accessible with the stimulated-echo pathway.     

Enhanced sensitivity to molecular diffusion with intermolecular double-quantum coherences: implications and potential applications

Apparent molecular self-diffusion rates for (1)H intermolecular double-quantum coherences (iDQCs) were measured in solvents covering a wide range of intrinsic diffusion coefficients at 1.5, 9.4 and 14T, and water iDQC diffusion-weighted images were obtained at 1.5T in human brains and at 9.4T in rat brains. Conventional single quantum coherence (SQC) measurements were also made in the same samples. Experimental results indicate that iDQCs are approximately twice as sensitive to diffusion as SQC. A general theoretical expression was derived, and a model was proposed to explain the phenomenon. Potential applications in DWI and brain fMRI were also discussed.     

Reduction in radiation dose with reconstruction technique in the brain perfusion CT

The principal objective of this study was to verify the utility of the reconstruction imaging technique in the brain perfusion computed tomography (PCT) scan by assessing reductions in the radiation dose and analyzing the generated images. The setting used for image acquisition had a detector coverage of 40 mm, a helical thickness of 0.625 mm, a helical shuttle mode scan type and a rotation time of 0.5 s as the image parameters used for the brain PCT scan. Additionally, a phantom experiment and an animal experiment were carried out. In the phantom and animal experiments, noise was measured in the scanning with the tube voltage fixed at 80 kVp (kilovolt peak) and the level of the adaptive statistical iterative reconstruction (ASIR) was changed from 0% to 100% at 10% intervals. The standard deviation of the CT coefficient was measured three times to calculate the mean value. In the phantom and animal experiments, the absorbed dose was measured 10 times under the same conditions as the ones for noise measurement before the mean value was calculated. In the animal experiment, pencil-type and CT-dedicated ionization chambers were inserted into the central portion of pig heads for measurement. In the phantom study, as the level of the ASIR changed from 0% to 100% under identical scanning conditions, the noise value and dose were proportionally reduced. In our animal experiment, the noise value was lowest when the ASIR level was 50%, unlike in the phantom study. The dose was reduced as in the phantom study.     

Characterisation of erythrocyte shapes and sizes by NMR diffusion-diffraction of water: correlations with electron micrographs

The utility of ¹H nuclear magnetic resonance (NMR) diffusion-diffraction of water as a tool for characterising red cell shape was investigated. Experiments were conducted on various cell suspensions which contained different shapes/forms of erythrocytes prepared by manipulating the conditions of the suspension medium, such as osmolality, and altering metabolism to affect the adenosine triphosphate concentration. Abnormal red cells from patients with hereditary stomatocytosis and megaloblastic anemia were also studied in order to assess the practical application of this “new” technique. The results clearly show that NMR diffusion-diffraction is sensitive to very small changes in mean cell dimensions and that a “characteristic” q-space plot/profile can be ascribed to each erythrocyte form. It was also found that the homogeneity of the cell shape and/or size is an important factor that affects the intensity of the diffusion-diffraction peaks. This study demonstrates the potential of the NMR diffusion-diffraction technique as a diagnostic tool in hematology.     

Delayed myelination in a rhizomelic chondrodysplasia punctata case: MR spectroscopy findings

Rhizomelic chondrodysplasia punctata is a member of genetic peroxisomal disorders. Delayed myelination, which is probably related to the inadequacy of plasmalogens biosynthesis, is an important feature of this disorder. Direct assessment of neuropathologic aspects of RCDP syndrome such as neuronal degeneration and delayed myelination is possible with MR spectroscopy.In this report, MR spectroscopy findings (decreased Cho/Cr and increased Ins-Gly/Cr ratios and increased levels of mobile lipids) of a rhizomelic chondrodysplasia punctata case supporting delayed myelination are presented. This is the second report of MR spectroscopy examination of the specific brain metabolic changes associated with rhizomelic chondrodysplasia punctata.     

Efficacy of magnetic resonance diffusion tensor imaging and three-dimensional fiber tractography in the detection of clinical manifestations of central nervous system lupus

Systemic lupus erythematosus (SLE) is an autoimmune disease frequently associated with neuropsychiatric manifestations. No follow-up case report has characterized white matter alterations in patients with neuropsychiatric lupus erythematosus (NPSLE) before and after treatment. In this study, a 16-year-old NPSLE patient with severe neuropsychological symptoms was treated with steroid pulse therapy, and was scanned with conventional magnetic resonance (MR) and diffusion tensor imaging (DTI) at onset and 17 months after treatment. Conventional MR images showed diffuse brain atrophy and focal vasogenic edema in the putamen, but they did not reveal abnormalities in the corpus callosum. Region-of-interest analysis of DTI images showed that fractional anisotropy and fiber tracts increased significantly, while axial diffusivity, radial, and mean diffusivity decreased significantly in the corpus callosum after treatment. The results indicated that the vasogenic edema was present in the corpus callosum at onset and was significantly reduced after treatment. These changes were generally compatible with the patient’s clinical manifestations. Hence, we concluded that MR-DTI and fiber tractography are helpful to reveal the relationship between white matter alterations and neurological dysfunctions in NPSLE patients.     

Validation of practical diffusion approximation for virtual near infrared spectroscopy using a digital head phantom

Light propagation in the digital head phantom for virtual near infrared spectroscopy and imaging is calculated by diffusion theory. In theory, diffusion approximation is not valid in a low-scattering cerebrospinal fluid (CSF) layer around the brain. The optical path length and spatial sensitivity profile predicted by the finite element method based upon the diffusion theory are compared with those predicted by the Monte Carlo method to validate a practical implementation of diffusion approximation to light propagation in an adult head. The transport scattering coefficient of the CSF layer is varied from 0.01 to 1.0 mm⁻¹ to evaluate the influence of that layer on the error caused by diffusion approximation. The error is practically ignored and the geometry of the brain surface such as the sulcus structure in the digital head phantom scarcely affects the error when the transport scattering coefficient of the CSF layer is greater than 0.3 mm⁻¹.     

The effect of the rotational angle on MR diffusion indices in nerves: is the rms displacement of the slow-diffusing component a good measure of fiber orientation?

In recent years, much effort has been made to increase our ability to infer nerve fiber direction through the use of diffusion MR. The present study examines the effect of the rotational angle (alpha), i.e. the angle between the diffusion sensitizing gradients and the main axis of the fibers in the nerves, on different NMR indices. The indices examined were the apparent diffusion coefficient (ADC), extracted from low b-values (b(max) approximately 1200 s/mm(2)), and the root mean square (rms) displacement of the fast and the slow-diffusing components extracted from high b-value q-space diffusion MR data. In addition, the effect of both the diffusion time and myelination was evaluated. We found that the most sensitive index to the rotational angle is the rms displacement of the slow-diffusing component extracted from the high b-value q-space diffusion MR experiment. For this component the rms displacement was nearly constant for alpha values ranging from -10 degrees to +80 degrees (where alpha=0 degrees is the z direction), but it changed dramatically when diffusion was measured nearly perpendicular to the nerve fiber direction, i.e., for alpha=90+/-10 degrees. The ADC and the rms displacement of the fast-diffusing component exhibited only gradual changes, with a maximal change at alpha=45+/-15 degrees. The sensitivity of the rms displacement of the slow-diffusing component to the rotational angle was found to be higher at longer diffusion times and in mature fully myelinated nerves. The relevance of these observations for determining the fiber direction is briefly discussed.     

In vivo MRI reveals the dynamics of pathological changes in the brains of cathepsin D-deficient mice and correlates changes in manganese-enhanced MRI with microglial activation

Cathepsin D (CTSD; EC 3.4.23.5) is essential for normal development and/or maintenance of neurons in the central nervous system: its deficiency causes a devastating neurological disorder with severely shortened life span in man, sheep and mouse. Neuropathologically, the CTSD deficiencies are characterized by selective neuronal degeneration, gliosis and accumulation of autofluorescent proteinaceous storage material in neurons. Our aim was to study the dynamics behind the pathological alterations occurring in the brains of CTSD-deficient (CTSD-/-) mice by using in vivo magnetic resonance imaging (MRI) and histology. In order to do this, we measured T(2) signal intensity (SI), apparent diffusion coefficient, area and volume of multiple brain structures from MR images acquired using T(2)-, T(1)- and diffusion-weighted sequences at three time points during disease progression. MRI revealed no differences in the brains between CTSD-/- and control mice at postnatal day 15+/-1 (P15+/-1), representing an initial stage of the disease. In the intermediate stage of the disease, P19(+/-1), SI alterations in the thalami of the affected mice became evident in both T(1)- and T(2)-weighted images. The terminal stage of the disease, P25, was characterized by marked alterations in the T(2) SI, apparent diffusion coefficient and volume of multiple brain structures in CTSD-/- mice. In addition, manganese enhanced high-resolution T(1)-weighted 3D sequences (MEMRI) and histological stainings revealed that the hyperintense signal areas in MEMRI matched perfectly with areas of microglial activation in the brains of CTSD-/- mice at the terminal disease stage. In conclusion, the SI alterations in the thalami of CTSD-/- mice preceded other changes, and the degenerative process was greatly enhanced at the age P19(+/-1), leading to severely reduced brain volume in just 6 days.     

Spatio-temporal anomalous diffusion imaging: results in controlled phantoms and in excised human meningiomas

Recently, we measured two anomalous diffusion (AD) parameters: the spatial and the temporal AD indices, called γ and α, respectively, by using spectroscopic pulse gradient field methods. We showed that γ quantifies pseudo-superdiffusion processes, while α quantifies subdiffusion processes. Here, we propose γ and α maps obtained in a controlled heterogeneous phantom, comprised of packed micro-beads in water and in excised human meningiomas. In few words, α maps represent the multi-scale spatial distribution of the disorder degree in the system, while γ maps are influenced by local internal gradients, thus highlighting the interface between compartments characterized by different magnetic susceptibility. γ maps were already obtained by means of AD stretched exponential imaging and α-type maps have been recently achieved for fixed rat brain with the aim of highlighting the fractal dimension of specific brain regions. However, to our knowledge, the maps representative of the spatial distribution of α and γ obtained on the same controlled sample and in the same excised tissue have never been compared. Moreover, we show here, for the first time, that α maps are representative of the spatial distribution of the disorder degree of the system.     

Assessment of scanner performance and normalization of estimated relaxation rate values

The purpose of this study was to develop and test a method for the assessment of Magnetic Resonance (MR) scanner performance suitable for routine brain MR studies and for normalization of calculated relaxation times. We hypothesized that regular monitoring of machine performance changes could provide a helpful normalization tool for calculating tissue MR parameters, thus contributing to support their use for longitudinal and comparative studies of both normal and diseased tissues.The method is based on the acquisition of phantom images during routine brain studies with standard spin-echo sequences. MR phantom and brain tissue parameters were used to assess the influence of machine related changes on relaxation parameter estimates. Experimental results showed that scanner performance may affect relaxation rate estimates. Phantom and in vivo results indicate that the correction method yields a reduction in variability of estimated phantom R1 values up to 29% and of R1 for different brain structures up to 17%. These findings support the validity of using brain coil phantoms for routine system monitoring and correction of tissue relaxation rates.     

Determination of Very Slow Diffusion of Paramagnetic Ions by NMR Spectroscopy

In this paper, we propose a new method of measuring the very slow paramagnetic ion diffusion coefficient using a commercial high-resolution spectrometer. If there are distinct paramagnetic ions influencing the hydrogen nuclear magnetic relaxation time differently, their diffusion coefficients can be measured separately. A cylindrical phantom filled with Fricke xylenol gel solution and irradiated with gamma rays was used to validate the method. The Fricke xylenol gel solution was prepared with 270 Bloom porcine gelatin, the phantom was irradiated with gamma rays originated from a ⁶⁰Co source and a high-resolution 200 MHz nuclear magnetic resonance (NMR) spectrometer was used to obtain the phantom ¹H profile in the presence of a linear magnetic field gradient. By observing the temporal evolution of the phantom NMR profile, an apparent ferric ion diffusion coefficient of 0.50 μm²/ms due to ferric ions diffusion was obtained. In any medical process where the ionizing radiation is used, the dose planning and the dose delivery are the key elements for the patient safety and success of treatment. These points become even more important in modern conformal radio therapy techniques, such as stereotactic radiosurgery, where the delivered dose in a single session of treatment can be an order of magnitude higher than the regular doses of radiotherapy. Several methods have been proposed to obtain the three-dimensional (3-D) dose distribution. Recently, we proposed an alternative method for the 3-D radiation dose mapping, where the ionizing radiation modifies the local relative concentration of Fe²⁺/Fe³⁺ in a phantom containing Fricke gel and this variation is associated to the MR image intensity. The smearing of the intensity gradient is proportional to the diffusion coefficient of the Fe³⁺ and Fe²⁺ in the phantom. There are several methods for measurement of the ionic diffusion using NMR, however, they are applicable when the diffusion is not very slow.     

MR assessment of the brain maturation during the perinatal period: quantitative T2 MR study in premature newborns

The purpose of our study is to trace in vivo and during the perinatal period, the brain maturation process with exhaustive measures of the T2 relaxation time values. We also compared regional myelination progress with variations of the relaxation time values and of brain signal. T2 relaxation times were measured in 7 healthy premature newborns at the post-conceptional age of 37 weeks, using a Carr-Purcell-Meiboom-Gill sequence (echo time 60 to 150 ms), on a 2.35 Tesla Spectro-Imaging MR system. A total of 62 measures were defined for each subject within the brain stem, the basal ganglia and the hemispheric gray and white matter. The mean and standard deviation of the T2 values were calculated for each location. Regional T2 values changes and brain signal variations were studied. In comparison to the adult ones, the T2 relaxation time values of both gray and white matter were highly prolonged and a reversed ratio between gray and white matter was found. The maturational phenomena might be regionally correlated with a T2 value shortening. Significant T2 variations in the brainstem (p < 0.02), the mesencephalon (p < 0.05), the thalami (p < 0.01), the lentiform nuclei (p < 0.01) and the caudate nuclei (p < 0.02) were observed at an earlier time than they were visible on T2-weighted images. In the cerebral hemispheres, T2 values increased from the occipital white matter to parietal, temporal and frontal white matter (p < 0.05) and in the frontal and occipital areas from periventricular to subcortical white matter (p < 0.01). Maturational progress was earlier and better displayed with T2 measurements and T2 mapping. During the perinatal period, the measurements and analysis of T2 values revealed brain regional differences not discernible with T2-weighted images. It might be a more sensitive indicator for assessment of brain maturation.     

Characterization of porous materials by small-angle scattering

Characterization of porous materials by small-angle scattering has been extensively pursued for several years now as the pores are often of mesoscopic size and compatible with the length scale accessible by the technique using both neutrons and X-rays as probing radiation. With the availability of ultra small-angle scattering instruments, one can investigate porous materials in the sub-micron length scale. Because of the increased accessible length scale vis-a-vis the multiple scattering effect, conventional data analysis procedures based on single scattering approximation quite often fail. The limitation of conventional data analysis procedures is also pronounced in the case of thick samples and long wavelength of the probing radiation. Effect of multiple scattering is manifested by broadening the scattering profile. Sample thickness for some technologically important materials is often significantly high, as the experimental samples have to replicate all its essential properties in the bulk material. Larger wavelength of the probing radiation is used in some cases to access large length scale and also to minimize the effect of double Bragg reflections.     

Water signal attenuation in diffusion-weighted 1H NMR experiments during cerebral ischemia: influence of intracellular restrictions,extracellular tortuosity,and exchange

The “concept of restricted intracellular water diffusion at permeable boundaries,” which was recently used to model diffusion-weighted ¹H NMR experiments on glioma cells, was applied to measurements on the rat brain in vivo. Combined with the “concept of extracellular tortuosity,” various physiological states of the brain were simulated. Hereby, a variable intracellular volume fraction, intracellular exchange time, and extracellular tortuosity factor were considered for young, adult, and ischemic rat brains. The model simulated the cytotoxic shift of extracellular water, changes in membrane permeability and tissue morphology, and was able to explain the diffusion time dependence as well as the non-monoexponentiality of the diffusion attenuation curves. Preliminary diffusion time dependent experiments on the healthy rat brain (¹H NMR imaging) agreed well with the theoretical concept. Hereby, the intracellular water signal was separated from extracellular signal contributions by large diffusion weighting. It showed the characteristic of restricted diffusion as well as a signal decay due to the exchange of intracellular water across the plasma membrane. A map of the mean intracellular exchange time for water in living animal brain was determined, and the upper limit in rat brain was evaluated to 15 ms. The presented methods can be applied to correlate local differences in a map of exchange times with tissue morphology and to detect pathological deviations of the exchange time, e.g., during ischemia.     

Crossing fibers, diffractions and nonhomogeneous magnetic field: correction of artifacts by bipolar gradient pulses

In recent years, diffusion tensor imaging (DTI) and its variants have been used to describe fiber orientations and q-space diffusion MR was proposed as a means to obtain structural information on a micron scale. Therefore, there is an increasing need for complex phantoms with predictable microcharacteristics to challenge different indices extracted from the different diffusion MR techniques used. The present study examines the effect of diffusion pulse sequence on the signal decay and diffraction patterns observed in q-space diffusion MR performed on micron-scale phantoms of different geometries and homogeneities. We evaluated the effect of the pulse gradient stimulated-echo, the longitudinal eddy current delay (LED) and the bipolar LED (BPLED) pulse sequences. Interestingly, in the less homogeneous samples, the expected diffraction patterns were observed only when diffusion was measured with the BPLED sequence. We demonstrated the correction ability of bipolar diffusion gradients and showed that more accurate physical parameters are obtained when such a diffusion gradient scheme is used. These results suggest that bipolar gradient pulses may result in more accurate data if incorporated into conventional diffusion-weighted imaging and DTI.     

A new automatic phase mask filter for high-resolution brain venography at 3 T: theoretical background and experimental validation

To improve vessel contrast in high-resolution susceptibility-based brain venography, an automatic phase contrast enhancing procedure is proposed, based on a new phase mask filter suitable for maximizing contrast of venous MR signals. The effectiveness of the new approach was assessed both on digital phantoms and on acquired MR human brain images, and then compared with venographic results of phase masking methods in recent literature. The digital phantom consisted of a simulated MR dataset with given signal-to-noise ratios (SNRs), while real human data were collected by scanning healthy volunteers with a 3.0-T MR system and a 3D gradient echo pulse sequence. The new phase mask (NM) was more effective than the conventional mask (CM) both on the digital phantoms and on the acquired MR images. A quantitative comparison based on phantom venograms indicates how this phase enhancement can lead to a significant increase in the contrast-to-noise ratio (CNR) for all considered phase values as well as for all vessel sizes of clinical interest. Likewise, the in vivo brain venograms reveal a better depiction of the smallest venous vessels and the enhancement of many details undetectable in conventional venograms.     

Insights into brain microstructure from the T2 distribution

T2 weighting is particularly sensitive, but notoriously unspecific, to a wide range of brain pathologies. However, careful measurement and analysis of the T2 decay curve from brain tissue promise to provide much improved pathological specificity. In vivo T2 measurement requires accurate 180 pulses and appropriate manipulation of stimulated echoes; the most common approach is to acquire multiple echoes from a single slice. The T2 distribution, a plot of component amplitude as a function of T2, can be estimated using an algorithm capable of fitting a multi-exponential T2 decay with no a priori assumptions about the number of exponential components. T2 distributions from normal brain show peaks from myelin water, intra/extracellular water and cerebral spinal fluid; they can be used to provide estimates of total water content (total area under the T2 distribution) and myelin water fraction (MWF, fractional area under the myelin water peak), a measure believed to be related to myelin content. Experiments on bovine brain suggest that magnetization exchange between water pools plays a minor role in the T2 distribution. Different white matter structures have different MWFs. In normal white matter (NWM), MWF is not correlated with the magnetization transfer ratio (MTR) or the diffusion tensor fractional anisotropy (FA); hence it provides unique information about brain microstructure. Normal-appearing white matter (NAWM) in multiple sclerosis (MS) brain possesses a higher water content and lower MWF than controls, consistent with histopathological findings. Multiple sclerosis lesions demonstrate great heterogeneity in MWF, presumably due to varying myelin contents of these focal regions of pathology. Subjects with schizophrenia were found to have significantly reduced MWF in the minor forceps and genu of the corpus callosum when compared to controls, suggesting that reduced frontal lobe myelination plays a role in schizophrenia. In normal controls, frontal lobe myelination was positively correlated with both age and education; this result was not observed in subjects with schizophrenia. A strong correlation between MWF and the optical density from the luxol fast blue histological stain for myelin was observed in formalin-fixed brain, supporting the use of the MWF as an in vivo myelin marker.