Silvia Capuani

Non-Gaussian diffusion imaging: a brief practical review

The departure from purely mono-exponential decay of the signal, as observed from brain tissue following a diffusion-sensitized sequence, has prompted the search for alternative models to characterize these unconventional water diffusion dynamics. Several approaches have been proposed in the last few years. While multi-exponential models have been applied to characterize brain tissue, several unresolved controversies about the interpretations of the results have motivated the search for alternative models that do not rely on the Gaussian diffusion hypothesis. In this brief review, diffusional kurtosis imaging (DKI) and anomalous diffusion imaging (ADI) techniques are addressed and compared with diffusion tensor imaging. Theoretical and experimental issues are briefly described to allow readers to understand similarities, differences and limitations of these two non-Gaussian models. However, since the ultimate goal is to improve specificity, sensitivity and spatial localization of diffusion MRI for the detection of brain diseases, special attention will be paid on the clinical feasibility of the proposed techniques as well as on the context of brain pathology investigations.

Anisotropic anomalous diffusion assessed in the human brain by scalar invariant indices.

A new method to investigate anomalous diffusion in human brain, inspired by the stretched‐exponential model proposed by Hall and Barrick, is proposed here, together with a discussion about its potential application to cerebral white matter characterization. Aim of the work was to show the ability of anomalous diffusion indices to characterize white matter structures, whose complexity is only partially accounted by diffusion tensor imaging indices. MR signal was expressed as a stretched‐exponential only along the principal axes of diffusion; whereas, in a generic direction, it was modeled as a combination of three stretched‐exponentials. Indices to quantify the tissue anomalous diffusion and its anisotropy, independently of the experiment reference frame, were derived. Experimental results, obtained on 10 healthy subjects at 3T, show that the new parameters are highly correlated to intrinsic local geometry when compared with Hall and Barrick indices. Moreover, they offer a different contrast in white matter regions when compared with diffusion tensor imaging. Specifically, the new indices show a higher capability to discriminate among areas of the corpus callosum associated to different distribution in axonal densities, thus offering a new potential tool to detect more specific patterns of brain abnormalities than diffusion tensor imaging in the presence of neurological and psychiatric disorders. Magn Reson Med, 2010.

Characterization of trabecular bone by dipolar demagnetizing field MRI

A multiple spin‐echo (MSE) sequence has been applied for the first time to study trabecular bone ex vivo. The second echo generated by the demagnetizing field presents discrete drops in signal intensity for certain values of the pitch of the magnetization helix created by the correlation gradient. These dips may reflect characteristic pore sizes in the trabecular bone specimens. This hypothesis is supported by similar experiments performed on a phantom with uniform pore size distribution. Trabecular bone images weighted in the MSE contrast mechanism are reported. Magn Reson Med 46:683–689, 2001.

Spatio-temporal anomalous diffusion in heterogeneous media by nuclear magnetic resonance

In this paper, we describe nuclear magnetic resonance measurements of water diffusion in highly confined and heterogeneous colloidal systems using an anomalous diffusion model. For the first time, temporal and spatial fractional exponents, α and μ, introduced within the framework of continuous time random walk, are simultaneously measured by pulsed gradient spin-echo NMR technique in samples of micro-beads dispersed in aqueous solution. In order to mimic media with low and high level of disorder, mono-dispersed and poly-dispersed samples are used. We find that the exponent α depends on the disorder degree of the system. Conversely, the exponent μ depends on both bead sizes and magnetic susceptibility differences within samples. The new procedure proposed here may be a useful tool to probe porous materials and microstructural features of biological tissue.

Water diffusion anisotropy in white and gray matter of the human spinal cord

To develop a reliable technique for diffusion imaging of the human spinal cord at 1.5 Tesla and to assess potential differences in diffusion anisotropy in cross‐sectional images.

In vitro and in vivo MR evaluation of internal gradient to assess trabecular bone density

Here we propose a new magnetic resonance (MR) strategy based on the evaluation of internal gradient (G(i)) to assess the trabecular bone (TB) density in spongy bone. Spongy bone is a porous system characterized by a solid trabecular network immersed in bone marrow and characterized by a different relative percentage of water and fats. Using a 9.4 T MR micro-imaging system, we first evaluated the relative water and fat G(i) as extracted from the Spin-Echo decay function in vitro of femoral head samples from calves. Indeed, the differential effects of fat and water diffusion result in different types of G(i) behavior. Using a clinical MR 3T scanner, we then investigated in vivo the calcanei of individuals characterized by different known TB densities. We demonstrate, on these samples, that water is more prevalent in the boundary zone, while fats are rearranged primarily in the central zone of each pore. In vitro experiments showed that water G(i) magnitude from the samples was directly proportional to their TB density. Similar behavior was also observed in the clinical measures. Conversely, fat G(i) did not provide any information on spongy-bone density. Our results suggest that water G(i) may be a reliable marker to assess the status of spongy bone.

L-DOPA PRELOADING INCREASES THE UPTAKE OF BOROPHENYLALANINE IN C6 GLIOMA RAT MODEL: A NEW STRATEGY TO IMPROVE BNCT EFFICACY

PURPOSE Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on (10)B(n,alpha)(7)Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of (10)B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for (10)B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first performed in vitro and then extended to the animal model. METHODS AND MATERIALS BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectroscopy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All animals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. RESULTS L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. CONCLUSIONS This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms.

13C CPMAS NMR spectroscopic analysis applied to wood characterization

Solid-state nuclear magnetic resonance (NMR) spectroscopic analysis were carried out on recent and archaeological wood. Cross-polarization-magic-angle spinning13C NMR spectra obtained from samples of poplar (Populus sp.), oak (Quercus sp.), and silver fir (Abies alba) were examined in this study. The most relevant peaks were assigned according to the extensive literature in the area, and the differences observed discussed in terms of lignin and cellulose composition: by fixing a lignin reference signal intensity, the cellulose and hemicellulose moieties showed a strong depletion compared to the lignin signals in archaeological wood.

In vivo 19F MRI and 19F MRS of 19F- labelled boronophenylalanine-fructose complex on a C6 rat glioma model to optimize boron neutron capture therapy (BNCT)

Boron neutron capture therapy (BNCT) is a promising binary modality used to treat malignant brain gliomas. To optimize BNCT effectiveness a non-invasive method is needed to monitor the spatial distribution of BNCT carriers in order to estimate the optimal timing for neutron irradiation. In this study, in vivo spatial distribution mapping and pharmacokinetics evaluation of the (19)F-labelled boronophenylalanine (BPA) were performed using (19)F magnetic resonance imaging ((19)F MRI) and (19)F magnetic resonance spectroscopy ((19)F MRS). Characteristic uptake of (19)F-BPA in C6 glioma showed a maximum at 2.5 h after compound infusion as confirmed by both (19)F images and (19)F spectra acquired on blood samples collected at different times after infusion. This study shows the ability of (19)F MRI to selectively map the bio-distribution of (19)F-BPA in a C6 rat glioma model, as well as providing a useful method to perform pharmacokinetics of BNCT carriers.

Fractional Order Generalization of Anomalous Diffusion as a Multidimensional Extension of the Transmission Line Equation

In this paper, a new fractional order generalization of the diffusion equation is developed to describe the anisotropy of anomalous diffusion that is often observed in brain tissues using magnetic resonance imaging (MRI). The new model embeds three different fractional order exponents-corresponding to the principal directions of water diffusion-into the governing Bloch-Torrey equation. The model was used to analyze diffusion weighted MRI data acquired from a normal human brain using a 3T clinical MRI scanner. Analysis of the data revealed normal Gaussian diffusion in the cerebral spinal fluid (isotropic fractional order exponent of (0.90 ±0.1), and anomalous diffusion in both the white (0.67 ±0.1) and the gray (0.77 ±0.1) matter. In addition, we observed anisotropy in the fractional exponent values for white mater (0.59 ±0.1) along the fibers versus 0.68 ±0.1 across the fibers), but not for gray matter. This model introduces new parameters to describe the complexity of the tissue microenvironment that may be sensitive biomarkers of the structural changes arising in neural tissues with the onset of disease.