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Spatial susceptibility variations of body components lead to local gradients of the static magnetic field. Effects of such background gradients on fractional diffusion anisotropy (FA) measurements on whole-body magnetic resonance units operating at 1.5, 3.0 and 7.0 T were analyzed theoretically and experimentally. Analytical expressions were derived for the cases of diffusion occurring in isotropic media and in tissues with cylindrical symmetry (e.g., white matter tracts or skeletal musculature). Typical magnitudes of background gradient strengths were estimated from in vivo and in vitro measurements with B-0 field mapping sequences. Additionally, numerical simulations of magnetic field distributions and resulting field gradients were performed considering tissue-air interfaces in simplified geometrical arrangements. For media with isotropic diffusion, both measurements and analytical calculations showed increasing FA inaccuracy with stronger coupling between diffusion-encoding and background gradients. For cylindrical symmetry, FA values were estimated for a standard diffusion tensor imaging protocol in a realistic scenario. At 1 mm distance from a water-air inter-face, susceptibility-related background gradients amount to approximately 9 mT/m at 7 T and lead to a relative error of the measured FA of up to 48%. The error in the anisotropy assessment rises considerably with increasing field strength and must be taken into account especially for experimental and clinical studies on modem high-field systems. (c) 2008 Elsevier Inc. All rights reserved.

Boron neutron capture therapy (BNCT) is a binary radiation therapy used to treat malignant brain tumors. It is based on the nuclear reaction (B-10 + n(th) -> [B-11*]-> alpha + Li-7 + 2.79 MeV) that occurs when B-10 captures a thermal neutron to yield alpha particles and recoiling Li-7 nuclei, both responsible of tumour cells destruction by short range and high ionization energy release. The clinical success of the therapy depends on the Selective accumulation of the B-10 carriers in the tumour and on the high thermal neutron capture cross-section of B-10. Magnetic resonance imaging (MRI) methods provide the possibility of monitoring, through B-10 nuclei, the metabolic and physiological processes suitable to optimize the BNCT procedure. In this study, spatial distribution mapping of borocaptate (BSH) and 4-boronophenylalanine (BPA), the two boron carriers used in clinical trials, has been obtained. The BSH map in excised rat brain and the F-19-BPA image in vivo rat brain, representative of BPA spatial distribution, were reported. The BSH image was obtained by means of double resonance B-10-editing H-1-detection sequence, named M-Bend, exploiting the J-coupling interaction between B-10 and H-1 nuclei. Conversely, the BPA map was obtained by F-19-BPA using F-19-MRI. Both images were obtained Lit 7 T, in C6 glioma-bearing rat brain. Our results demonstrate the powerful of non conventional MRI techniques to optimize the BNCT procedure. (C) 2008 Elsevier Inc. All rights reserved.

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 F-19-labelled boronophenylalanine (BPA) were performed using F-19 magnetic resonance imaging (F-19 MRI) and F-19 magnetic resonance spectroscopy (F-19 MRS). Characteristic uptake of F-19-BPA in C6 glioma showed a maximum at 2.5 h after compound infusion as confirmed by both F-19 images and F-19 spectra acquired on blood samples collected at different times after infusion. This study shows the ability of F-19 MRI to selectively map the bio-distribution of F-19-BPA in a C6 rat glioma model, as well as providing a useful method to perform pharmacokinetics of BNCT carriers.

Reaction yield optimization for the synthesis and the complexation of a boron neutron capture therapy agent F-19-labelled, B-10-enriched p-boronophenylalanine-fructose (F-19-BPA-fr) complex was obtained. H-1, F-19, C-13 and B-10 magnetic resonance spectroscopy (MRS) of the F-19-BPA-fr complex in aqueous and rat blood solution phantoms and its spatial distribution mapping using F-19 magnetic resonance imaging (MRI) results are reported. 7 T and 9.4 T magnetic fields were used to perform MRI and MRS respectively. Our in vitro results suggest that in vivo studies on F-19-BPA through F-19 NMR will be feasible.

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. (C) 2011 Elsevier Inc. All rights reserved.

In the present work, an arteriovenous malformation was taken as a pathological model for studying task-related flow decreases during a motor task. Combined Blood Oxygen Level Dependent (BOLD)-perfusion experiments were applied in order to evaluate the relative sensitivity of these techniques to task-related reductions in cerebral blood flow (CBF). Results shows that, by matching the sensitivity of the methods (which exhibit a different contrast-to-noise ratio) in the primary motor cortex, the spatial extent of the regions of decreased perfusion signal is larger than those of the BOLD signal reduction. The above finding suggests that perfusion imaging, that already represents a gold standard method in the detection of vascular phenomena, may estimate task-related flow decreases in a functional time-series better than BOLD.

Prostate cancer (PC) is one of the most common diseases in western countries and a leading cause of cancer death. A variety of treatment options are available but a precise disease characterization is needed: evaluation of cancer location, size, and extent and an indication of tumor aggressiveness. The current standard for diagnosing PC is transrectal ultrasound guided sextant biopsy. A novel multidisciplinary approach is required. Imaging may play a key role provided that dedicated prostate imagers and procedures are available: considerable improvements have been achieved in diagnosis with the Magnetic Resonance Imaging (MRI) and nuclear medicine (Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT)) techniques. Nevertheless, due to sub-optimal prostate imaging geometries with these generic large instruments preventing separation of the signal from surrounding organs, the sensitivity, spatial resolution and lesion contrast detected are lower compared to what can be potentially achievable with optimized dedicated prostate imagers and procedures. Fully exploiting the Time Of Flight (TOF) capability would allow not only to increase the Signal-to-Noise ratio (SNR) / Noise Equivalent Count Rate (NECR) but also to get rid of the huge background coming from neighboring organs i.e. the bladder. Recently a new research project was initiated by a large INFN collaboration, and a “TOF-PET and MRI for prostate cancer diagnosis and follow up experiment” (TOPEM) was financed as a 3-year experiment by the Italian “INFN Commissione Scientifica Nazionale V” with the goal of designing, building and testing in phantom tests an endorectal PET-TOF probe compatible with MRI.

Recently, we measured two anomalous diffusion (AD) parameters: the spatial and the temporal AD indices, called gamma and alpha, respectively, by using spectroscopic pulse gradient field methods. We showed that y quantifies pseudo-superdiffusion processes, while a quantifies subdiffusion processes. Here, we propose gamma and alpha maps obtained in a controlled heterogeneous phantom, comprised of packed micro-beads in water and in excised human meningiomas. In few words, alpha maps represent the multi-scale spatial distribution of the disorder degree in the system, while y maps are influenced by local internal gradients, thus highlighting the interface between compartments characterized by different magnetic susceptibility. gamma maps were already obtained by means of AD stretched exponential imaging and alpha-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 alpha and gamma 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 a maps are representative of the spatial distribution of the disorder degree of the system.In a first phase, gamma and alpha maps of controlled phantom characterized by an ordered and a disordered rearrangement of packed micro-beads of different sizes in water and by different magnetic susceptibility (Delta chi) between beads and water were obtained. In a second phase, we investigated excised human meningiomas of different consistency.Results reported here, obtained at 9.4T, show that alpha and gamma maps are characterized by a different image contrast. Indeed, unlike y maps, a maps are insensible to (Delta chi) and they are sensible to the disorder degree of the microstructural rearrangement. These observations strongly suggest that AD indices alpha and gamma reflect some additional microstructural information which cannot be obtained using conventional diffusion methods based on Gaussian diffusion. Moreover, alpha and gamma maps obtained in excised meningiomas seem to provide more microstructural details above those obtained with conventional DTI analysis, which could be used to improve the classification of meningiomas based on their consistency. (C) 2013 Elsevier Inc. All rights reserved.

A new method to investigate anomalous diffusion in human brain is proposed. The method has been inspired by both the stretched-exponential model proposed by Hall and Barrick (HB) and DTI. Quantities extracted using HB method were able to discriminate different cerebral tissues on the basis of their complexity, expressed by the stretching exponent gamma and of the anisotropy of gamma across different directions. Nevertheless, these quantities were not defined as scalar invariants like mean diffusivity and fractional anisotropy, which are eigenvalues of the diffusion tensor. We hypotesize instead that the signal may be espressed as a simple stretched-exponential only along the principal axes of diffusion, while in a generic direction the signal is modeled as a combination of three different stretched-exponentials. In this way, we derived indices to quantify both the tissue anomalous diffusion and its anisotropy, independently of the reference frame of the experiment. We tested and compare our new method with DTI and HB approaches applying them to 10 healty subjects brain at 3T. Our experimental results show that our parameters are highly correlated to intrinsic local geometry when compared to HB indices. Moreover, they offer a different kind of contrast when compared to DTI outputs. Specifically, our indices show a higher capability to discriminate among different areas of the corpus callosum, which are known to be associated to different axonal densities., Comment: 21 pages, 6 figures, 2 tables

"Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on B-10(n, alpha)Li-7 reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of B-10 nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for B-10-drug 4-dihydroxy-borylphenylaianine (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. (C) 2008 Elsevier Inc."

The distribution of two main Boron neutron capture therapy (BNCT) agents, borocaptate sodium ( BSH ) and borono-phenylalanine ( BPA ), in C6 rat glioma cells has been investigated by means of radiowave dielectric spectroscopy measurements. Significant differences between cells treated with the two different boron carriers were found in the magnitude of passive electrical cell parameters. This technique offers a new procedure for the measurement of boron compounds interactions with different biological environments at cellular level and is suggested to have the potentiality for becoming an attractive tool for biodistribution studies of BNCT compounds in biological tissues.