Congresso scientifico organizzatodall’Associazione Italiana di Risonanza Magnetica in Medicina edall’Italian Chapter dell’ISMRM

Risonanza Magnetica in Medicina 2013:

dalla ricerca tecnologica avanzataalla pratica clinica

PERUGIA, 24 - 25 ottobre 2013

Programma

4° Congresso Annuale dell'Italian Chapter dell'ISMRM

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MRI MONITORING OF DISEASE IN A MOUSE MODEL OF COLITIS

M. Russo1, L. Fiandra2, S. Cribioli1, M. Ciomei1, E. Pesenti1, F. Corsi 3, A. Degrassi1

1Pharmacology Department, BU Oncology, Nerviano Medical Sciences, Nerviano, MI2Ospedale L. Sacco, Milan3Clinical and Biomedical Sciences Department “Luigi Sacco”, University of Milan

Introduction: Inflammatory bowel disease (IBD), including ulcerative colitis, is characterized by persistent or recurrent in-flammation and can progress to colon cancer. Colitis is difficult to detect and monitor noninvasively. The aim of this workwas to set up a preclinical MR imaging method for characterization of chemically-induced acute colitis.Methods: Administration of dextran sulfate sodium (DSS) in drinking water induces a dose-dependent and time-dependentreversible form of colitis in mice(1). In this study C57BL/6J mice had ad libitum access to drinking water containing 3%DSS for 7 days. Since weight loss and subsequent gain profiles are useful indicators of DSS-induced IBD progression,mice were weighted twice weekly until dosing begins, and daily thereafter.MRI was performed on a 7T Bruker Phamascan at day 3, 5 and 7. A series of 3D-FLASH sequences were used, beforeand after intravenous injection of a Gd-based contrast agent (Gadovist®, Bayer). Sequence parameters were as follows:TR/TE 16.8/5.4 ms, isotropic resolution: 0.2 mm/pixel, 10 av , tot. scan time: 12 min.Results: All mice exposed to 5 days of DSS developed acute inflammation of various grades, as depicted by clinical symp-toms such as body weight loss, fecal blood and lose fecal consistency. When compared with controls, only DSS treatedmice showed progressive signal enhancement of colonic wall after Gd injection. Depending on time from beginning of DSStreatment, different intestinal areas appeared to be subsequently involved. At early time points small intestinal walls showedsome degree of enhancement, while at late time points colon and rectum appeared to be the most affected areas. In themost severe cases the contrast medium diffused from the intestinal wall to the lumen.Conclusions: High resolution Gd-enhanced MRI was able to detect inflammation of the colonic wall and monitor diseaseprogression. In alternative, new molecular targeted contrast agents could also be used to further characterize this model.This non-invasive approach offers a powerful tool for efficacy evaluation of novel compounds in preclinical models of IBD.(1) Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murinecolitis. Lab Invest 1993;69:238–249.

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Environmental enrichment modulates individual response to cannabinoid administration in mice: a 1 H MRS study

L. Altabella1, C. Ceci1, S. Macrì1, R. Canese1, G. Laviola1

1Dip. Biologia Cellulare e Neurosceinze, Istituto Superiore di Sanità, Roma

Clinical and experimental studies indicate that the effects of the consumption of psychoactive drugs may be modulatedby adverse or stimulating environmental conditions. The hypothalamic-pituitary-adrenal (HPA) and the endocannabinoid

system (ECS) interact to modulate the expression of emotions. Here we analysed by 1 H MRS in CD1 adult mice howexposure to stimulating environments (EE) compared to traditional animal facility rearing (AFR) during development mo-dulates individual response to the administration of an ECS agonist during adolescence (JWH-018, 0.3 mg/kg).1 H MRS experiments were performed in adult mice on a VARIAN Inova MRI/MRS system operating at 4.7T. 1 H localised

MR spectra were collected from the hippocampus (HIP, 11.7 µl) and prefrontal cortex (PFC, 5.9 µl) using PRESS sequence(TR/TE = 4000/23 ms, ns = 256 or 512 for each voxel respectively). According to a quantitative protocol [1] which includeswater T2 measurements, spectra were analysed by using LCModel fitting program [2] and the unsuppressed water signalfor metabolite quantification. Alterations in brain metabolite concentrations have been found between the groups in bothregions. In PFC we find interaction effects for the following metabolites: tCho (p<0.0001), tNAA (p=0.003) and total creatine(tCr, p=0.01). For all these metabolites EE reverts the effect of the JWH-018 treatment. Also in Hip tNAA shows the sametrend (p=0.04) while the Glu significantly increases in JWH-018-treated animals (p=0.01). Principal Component Analysis(PCA) extracted three orthogonal factors in both regions analysed. Results showed that environmental enrichment radicallymodified the effects of JWH-018 administration on brain metabolism. This study underlines how rearing conditions maystrongly influence individual reactivity, and in turn its vulnerability, towards the effects of psychoactive compounds.[1] Canese et al NMR Biomed 2012.[2] Provencher Magn Reson Med 1993.

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PLASTICITY OF BROWN AND WHITE ADIPOSE TISSUE IN MICE DUE TO HIGH FAT DIET AND CONCOMITANT

PHARMACOLOGICAL TREATMENTS WITH MINERALOCORTICOID RECEPTOR ANTAGONISTS: AN IN VIVO 1HMRI/MRS STUDY

R. Canese1, F. Cinti2, A. Armani2, V. Marzolla2, F. Ginnari Satriani1, G. Carpinelli1, M. Caprio2

1Dept. of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy2Lab. of Cardiovascular Endocrinology, IRCSS San Raffaele Pisana, Rome, Italy

Brown adipose tissue (BAT) is currently a topic of interest in obesity and metabolic research due to its physiological re-levance in human adults. White adipocytes are characterized by large uni-locular intracellular lipid droplet and reducedcytoplasm, brown adipocytes are endowed with multiple, smaller, intracellular lipid droplets and are extremely rich in mito-chondria. Aim of the study was to monitor by localized 1H MRS and MRI changes in adipose tissue as a result of high fatand concomitant pharmacological treatment with mineralocorticoid receptor (MR) antagonists, drospirenone (DRSP) andspironolactone (Spiro), in inguinal and perivescical fat depots.C57bl6 female mice were fed normal chow (ND) or a high fat (HF) diet for 12 weeks. Mice fed HF were concomitantly treatedfor 12 weeks with either vehicle, DRSP or Spiro. After 12 weeks coronal and axial multislice spin echo images were acquiredfrom the abdomen for quantitative evaluation of visceral fat volume. STEAM spectra have been acquired for water and lipidquantitative determination (by using LCModel for spectral fitting). An inversion recovery STEAM sequence was applied toacquire spectra at progressively longer TEs and TIs for T2 and T1 determination, respectively. MRI experiments showedsignificant differences between the volumes of DRSP-treated compared with HF diet group and Spiro-treated comparedwith HF-treated group. Both the treatments counteracted the increase in fat volumes due to high fat diet. MRS analyses onfat depots showed significant differences in the ratio water/CH3 lipid signal at 0.9 ppm among the high fat diet groups andbetween DRSP- compared with HF-treated and Spiro- compared with HF-treated in inguinal but not in perivescical region.Also the percentage of water was significantly increased in the inguinal fat of DRSP- and Spiro- treated mice compared tocontrol animals, suggesting an increase in brown-like adipocytes, richer in water than white adipocytes.Our results are in agreement with histological analyses demonstrating that MR antagonists reversed HF diet-induced adi-pocyte hypertrophy, increased brown-like adipocyte content of white adipose tissue (WAT) depots (as detected by in vivoMRI/MRS) and improved the metabolic activity of adipose tissue, as shown by PET/CT studies.

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HIGH-RESOLUTION 7T EX VIVO MRI AND HISTOPATHOLOGY IN HUMAN HIPPOCAMPUS IN NORMAL CONDITIONAND HIPPOCAMPAL SCLEROSIS

R. Garbelli1, R. Coras2, G. Milesi1, I. Zucca3, A. Mastropietro3, A. Scotti3, M. Figini3, C. Frassoni1, G. Tringali4, I.

Blumcke2, R. Spreafico1

1Clinical Epileptology and Experimental Neurophysiology Unit, Fondazione I.R.C.C.S. Istituto Neurologico “C. Besta”,Milano, Italy2Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany3Scientific Department, Fondazione I.R.C.C.S. Istituto Neurologico “C. Besta”, Milano, Italy4Department of Neurosurgery, Fondazione I.R.C.C.S. Istituto Neurologico “C. Besta”, 20133 Milano, Italy

Hippocampal sclerosis (HS) is the major finding in patients with mesial temporal lobe epilepsy (MTLE). However, the internalstructure of hippocampus remains difficult to recognize at 1,5, 3 or 7Tesla magnetic resonance imaging (MRI) (Theyson etal., 2009). Aim of the present work is to delineate subregions and layers in normal and sclerotic human hippocampus bycomparing high-field 7T-MRI and corresponding histolo(patholo)gical sections.Human hippocampal specimens were admitted to different imaging protocols on a 7T scanner. Subsequent histologicalanalysis was performed to confirm MRI findings through the antero-posterior extent of the hippocampus. Fractional aniso-tropy maps (FA) and fibre track were used to visualize intrahippocampal projections and fibres bundles.In T2-weighted images from normal hippocampi, differences in signal intensity showed the internal hippocampal structureswith clearly recognizable layers. In all HS specimens, besides a global reduction of the whole hippocampus, MRI slicesshowed an increased signal intensity through CA1-3 sectors, regardless the histopathologic subtypes of HS. The hypersi-gnal and atrophy were not related to either the neuronal loss or gliosis. Moreover, in HS specimens was not possible todetect the hippocampal layers visualized in normal specimens. Intrahippocampal fibre tracts, as depicted by FA and colourfibres orientation maps, visible in normal specimens were not recognized in pathological specimens.The present data suggest that high resolution MR microcopy was able to identify anatomical subcompartments and su-blayers along the entire anterior-posterior hippocampal axis, and will be a promising tool for the investigation of subtle pa-thology in neurological or neurodegenerative disorders. Nevertheless, even in a ultra high field, with the present sequencesavailable is not possible to discriminate different subtypes of HS.Theysohn JM, Kraff O, Maderwald S, et al. The human hippocampus at 7 T-in vivo MRI. Hippocampus 2009;19:1-7.

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CHANGES IN LAMINAR ORGANIZATION IN THE HUMAN HIPPOCAMPUS FROM MIDGESTATION TO ADULTHOODREVEALED BY HISTOLOGICAL AND EX-VIVO 7T MRI APPROACHES

G. Milesi1, I. Zucca2, R. Garbelli1, E. Aronica 3, R. Spreafico1, C. Frassoni1

1Clinical Epileptology and Experimental Neurophysiology Unit, Fondazione I.R.C.C.S. Istituto Neurologico "C. Besta",Milan, Italy.2Scientific Department, Fondazione I.R.C.C.S. Istituto Neurologico "C. Besta", Milan, Italy:3Departement of Neuropathology, Academisch Medisch Centrum, Meibergreef, Amsterdam, Netherland.

During development the hippocampus undergoes numerous changes, both as regards the cytoarchitecture, the cellularmorphology and the mieloarchitecture which begin in the fetal period and continues after birth (Abraham et al., 2010). Aim ofthe present study is to investigate the developmental changes occurring in human healthy fetal and postnatal hippocampusby combining high-field 7T MRI and histological and immunohistochemical analysis. Fifteen preterm samples from 18 to 32gestational weeks (GW) and six postnatal specimens from 1 day to adulthood were scanned by a 7T MR scanner. Subse-quently, the samples were submitted to histological and immunohistochemical techniques to compare variations in signalintensity with cito- and myeloarchitectural organization. During fetal period the intensity of the T2-weighted images (T2-wi)is related to cellular density. In fact the subregions of Ammon’s horn and dentate gyrus, characterized by densely packedneurons, are easily recognizable on ex vivo high field MRI as hypointense areas. The inverse correlation between MRI si-gnal intensity and cellular density is supported by line profile results. At the age of two postnatal week, the low MRI signal isstill linked to the cell density even if thin myelinated fibers are observed in the alveus and in the str. lacunosum-moleculare.The myelin content increases more and more with advancing development till to get the complete hippocampal myeloar-chitecture in the adulthood. From 7 years until the adult, comparison between MRI and corresponding histological sectionsindicate that the differences in T2-wi reflect the increased density of myelinated fibers. In conclusion, our study shows thepotential utility of high-field MRI for detection of developmental changes in human fetal and postnatal hippocampus. Thesedata will be a promising tool in the understanding of hippocampal abnormalities occurring in developmental disorders whenin the future high resolution MRI can be used in clinical practice.H. Ábráham et al. Myelination in the human Hippocampal formation from midgestation to adulthood. Int.J Dev Neuroscience28: 401-410, 2010.

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OPTIMIZATION OF AN IN-VIVO ECHO PLANAR DIFFUSION TENSOR IMAGING (EPI-DTI) PROTOCOL TO STUDYTHE MOUSE SPINAL CORD OVER TIME AND APPLICATION TO AN AMYOTROPHIC LATERAL SCLEROSIS (ALS)MOUSE MODEL

I. Zucca1, A. Scotti1, M. Figini4, S. Marcuzzo2, P. Bernasconi2, R. Mantegazza2, S. Bonanno2, V. Moreno Manzano5, M.G.

Bruzzone3

1U.O. Direzione Scientifica, IRCCS Fondazione Istituto Neurologico Carlo Besta, Milano2U.O. Neurologia IV, IRCCS Fondazione Istituto Neurologico Carlo Besta, Milano3U.O. Neuroradiologia, IRCCS Fondazione Istituto Neurologico Carlo Besta, Milano4Dipartimento di Bioingegneria, Politecnico di Milano5Neuronal and Tissue Regeneration Laboratory, Prince Felipe Research Center, Valencia, SPAIN

DTI is a non-invasive modality employed extensively to characterize the spinal cord integrity. EPI is often used in humanstudy to reduce the acquisition time. In animal models of spinal cord diseases it is difficult to use single-shot EPI, due toincreased ghosting and susceptibility artifact at higher magnetic field. Our aims are to optimize an acquisition and processingprotocol for in-vivo DTI study on mouse spinal cord and to examine the potential of the DTI-derived parameters (fractional

anisotropy FA, longitudinal diffusivity λl, radial diffusivity λr and ADC) to study the time evolution of the pathology in G93A-SOD1, an ALS mouse model [C.K. Underwood et al., Neuroimage 2011].DTI experiments are carried out by 7T MRI scanner (Bruker BioSpec 70/30) in 4 WT and 4 G93A-SOD1 mice at sixtime points: 9,10,12,15,17,18 weeks (w). Two different Single-shot EPI-DTI acquisition protocols are performed. The first

consists of an EPI sequence with the following parameters: 126 gradient directions (dir), b=700 s/mm2 , 6 averages (NA),1 repetition (NR) and Acquisition Time(AT)=28min . The second protocol consists of two EPI sequences: one with 12 dir,

b=1200 s/mm2 , NA=4, NR=15 and AT=35 min; the other with 2 dir, b=200-400-800-1200-1500 s/mm2 , NA=4, NR=20 andAT=42 min. In each scan, 8 contiguous axial slices of the spinal cord at the lumbar level with slice thickness=0.8mm, in-

plane resolution=0.109x0.078 mm2, FOV=1.4x1 cm2 are obtained.

All the images are corrected for motion and distortions using FSL’s FLIRT. FA, λl, λr and ADC were estimated using ahome-made code in Matlab.The regions of interest are manually outlined: dorsal, ventral and ventro/dorsolateral white matter (WMd, WMv, WM-vl/WMdl), dorsal and ventral gray matter (GMd, GMv).Both the protocols provide a good anatomical view of the spinal tract, in terms of spatial resolution and image contrastand show a good reproducibility of the measures. However, while the first shows a reduced FA compared to WT mice in

WMv at 18w, the second detects such reduction 3 weeks before in all the regions. It also shows reduction in λl, increase

in λr at 17w and decrease in ADC in WMd and GM since 12w. The agreement of this protocol’s results with the electronmicroscopy findings prove it to be more adequate than the previous one to evaluate spinal cord damage.

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New insights into Anomalous-Diffusion image contrast in brain tissues

M. Cavalieri1, M. Palombo1, A. Gozzi3, A. Gabrielli2, A. Bifone3, S. Capuani1

1Dipartimento di Fisica, Università "Sapienza", Roma.2ISC-CNR, Roma.3Istituto Italiano di Tecnologia, Center for Nanotechnology Innovation IIT, Pisa.

PURPOSE:The departure from mono-exponential decay of the Pulsed Field Gradient signal as b- value's function in bio-logical tissues, prompted the research of alternative models for non-Gaussian dynamics of water diffusion. In this study

we investigate anomalous diffusion (AD) stretched exponential γ-imaging model1 based on fitting the stretched function

S(b)=S(0)exp(-(bD) #) to PFG data varying the gradient strength. The biophysical origin of the contrast in γ maps is relatedto water multi-compartmentalization and to internal gradients (g) at the interface between tissues characterized by different

∆χ. The aim of the present study was to obtain γ values in the intrinsic γ reference frame (γRF), to improve the γ mapsability to discriminate microstructural features in different brain tissues better than DTI maps. Moreover, we characterize

γRF showing how it differs from that of DTI RF.METHOD & EXPERIMENT: We hypothesized to identify a specific RF defined by the main directions of the anomalousdiffusion: in a three dimensional space it is always possible to decompose the motion into its projections along three main

axes. In a previous work1it was used a “first order approximation" in which γ is projected along the DTI main directions. Inour work, we remove this approximation: the signal is projecting along an intrinsic reference frame of anomalous diffusion .

The three γ values can be used to extract invariant indices, such as the mean γ (Mγ) and the anisotropy (Aγ). Two mousebrain were investigated (one fixed in paraformaldehyde and stored in PBS and another one in vivo). An imaging version of

PGSTE sequence was performed on an N MR scanner 7.0T with TE/TR = 25.77/4000, ∆/δ= 40/2, NA = 14; 16 axial slices

with STH= 0.75mm, FOV=6cm, in plane resolution of 470µm, 11 b-values ranging from 100 to 9000s/mm2 along 30 no-coplanar directions plus 5 b=0s/mm2 images was acquired.

RESULTS & CONCLUSION:The γ-maps projecting along γRF show a better discrimination among different anatomicalbrain regions and higher image quality compared to the maps obtained using DTI RF, providing micro-structural detailsnot approachable with conventional DTI.1)De Santis S. et al., Magn Res Med 2011;65:1043-1052

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The miswired brain: altered functional and structural connectivity in mouse models of autism

F. Sforazzini1, L. Dodero1, A. Galbusera1, A. Bifone1, M.L. Scattoni2, C. Gross3, A. Gozzi1

1Istituto Italiano di Tecnologia, Center for Neuroscience and Cognitive Systems @UniTn, Rovereto, Italy2Istituto Superiore di Sanità, Neurotoxicology and Neuroendocrinology Section, Department of Cell Biology andNeurosciences, Rome3Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy

Autism is a neuro-developmental condition characterized by impaired social interactions, deficits in language developmentand repetitive behaviours. MRI studies in autistic patients have revealed abnormal patterns of brain connectivity characte-rised by reduced white matter fractional anisotropy and impaired long-range functional connectivity.The application of translational measures of brain connectivity in mouse models of autism can help elucidate the elusiveneurophysiological determinants of these alterations. We recently described the use of high-resolution DTI and resting-stateBOLD fMRI to probe the neurofunctional architecture of the mouse brain. Here we show evidence of major structural andfunctional connectivity deficits in BTBR T+tf/J mice (BTBR), an inbred line that shows robust behavioural phenotypes withanalogies to all three diagnostics symptoms of autism. Specifically, DTI data highlighted callosal agenesis and lack ofhippocampal commissure in BTBR mice. These changes were associated to reduced intrinsic connectivity of frontal areaswith hippocampal and thalamic regions.In an attempt to probe a contribution of synaptic dysfunction to the connectivity alterations observed in autism, fMRI con-nectivity was also measured in Cx3cx KO mice, a line characterised by deficient synaptic pruning during early stage ofdevelopment, and exhibiting behavioural traits reminiscent of autism symptoms. Resting-state fMRI data revealed a speci-fic impairment of long-range fronto-hippocampal connectivity, and a trend for increased local connectivity in fronto-corticalareas. These findings suggest that impaired synaptic pruning is sufficient to induce autism-related functional connectivitydeficits.Collectively, these findings corroborate the use of MRI-based measures of brain connectivity to investigate the neuropa-thological origin of connectional alterations observed in clinical populations.

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Brain development during adolescence: metabolic, anatomical and functional characterisation in rats.

L. Altabella1, F. Zoratto2, F. De Pasquale3, G. Laviola1, W. Adriani1, R. Canese1

1Dip. Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Roma2Dip. Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Roma; Ospedale Pediatrico Bambino Gesù, Roma3ITAB, Dip. Neuroscienze e Imaging, Chieti

Brain undergoes several morphological and functional changes during adolescence, in humans as well as in rodents. Ma-gnetic resonance is the most suitable technique to study these changes in vivo because it can investigate brain metabolism

(by 1H MRS), anatomy (by DTI) and functionality (by functional connectivity) in a non-invasive way. Wistar male rats at early(PND 21-24, n=12), middle (PND 28-31, n=12) and late adolescence (PND 35-38, n=12) were considered. Experimentswere performed on a VARIAN Inova MRI/MRS system operating at 4.7 T, by using a volume coil as transmitter and asurface coil as receiver (RAPID Biomedical). Between early and middle adolescence, by quantitative MRS analysis [1] inhippocampus (HIP) we detected, using LCModel as fitting program [2], a significant increase of Inositol. Between middleand late adolescence, we detected an increase in total choline while taurine decreased. Our seed-based analysis in theconnectivity study found differences in the functional maps of networks among the three different ages. Specifically, asconsequence of the age-related development, an increase in the strength of connectivity was detected between early andmiddle or late adolescent for the analysed seeds (nucleus accumbens NAcc, orbital frontal cortex OFC and HIP in bothhemispheres). As an example, for a seed positioned in the right HIP, we found an increase in the number of areas whichare functionally connected and in the strength of such connection in late and in middle with respect to early adolescence.Preliminary analysis of DTI data shows a significant decrease of FA in the brains of animals at late compared to middleadolescence in both NAcc and OFC. Present data provide a deeper view on the metabolic, morphological and functionalmodifications which occur during rodents’ adolescence. The FA reduction suggest that important structural modificationhappen in the NAcc and OFC during adolescence. Finally, it is during adolescence that functional changes occur withinforebrain networks like maturation of cortico-limbic loops.[1] Canese et al., NMR Biomed 2012.[1] Provencher, Magn Reson Med 1993.

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Optimization of a threshold for tractography with NODDI

M. Figini1, B. Barra1, G. Castelli2, A. Bizzi3, H. Zhang4, G. Baselli1

1Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy2Neuroradiologia, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, Milano, Italy3Neuroradiologia, Istituto Clinico Humanitas IRCCS, Rozzano, Milano, Italy4Centre for Medical Image Computing, Department of Computer Science, University College London, London, UnitedKingdom

PURPOSE The standard Diffusion Magnetic Resonance Imaging (dMRI) technique in clinical research is Diffusion TensorImaging (DTI), but many model-based methods have been recently proposed aiming at a better characterization of micro-structure. Among them, NODDI [1] has the advantage of the feasibility in a clinical setting. In DTI-based tractography, athreshold on Fractional Anisotropy (FA) is often used for termination. The aim of this work is to find an equivalent thresholdfor the main parameter derived by NODDI, the Orientation Dispersion Index (ODI).METHODS dMRI data from a healthy subject were acquired on a 3T scanner (Siemens Verio, Erlangen, Germany) with 8 b= 0 volumes and 60 diffusion-weighted ones in 2 shells (b = 700 and 2000 s/mm2). Images were registered using FSL [2].NODDI and DTI parameters were estimated in each voxel using the NODDI Matlab Toolbox [3] and Diffusion Toolkit [4].The FA and ODI maps were compared and the relationship between the two parameters was investigated by fitting withdifferent mathematical functions. In a second stage, DTI-based whole-brain tractography was performed in Trackvis [4],using an FA threshold of 0.2 and using different ODI thresholds between 0.1 and 1; an angle threshold of 35° was applied inall the cases. From each reconstruction the corpus callosum (CC) and cortico-spinal tract (CST) were extracted. The Diceindex was calculated to quantify the overlapping between the tract obtained with each ODI threshold and the referenceone (FA = 0.2).RESULTS According to the analytical functions found in the fitting stage, the ODI value corresponding to FA = 0.2 is 0.45.From the second stage, we found an optimal ODI threshold of 0.45 for CC and 0.44 for CST. The tracts reconstructedfrom NODDI directions with the found threshold were very similar to those from the standard DTI procedure, with minimaldifferences in the marginal parts only.CONCLUSION In this preliminary work on tractography from NODDI data, we found an ODI threshold equivalent to thecommonly used FA = 0.2. This result could be important in clinical studies comparing DTI-based and NODDI-based trac-tography to understand if NODDI can allow reconstructing tracts more reliably in pathological conditions.[1] Zhang et al., Neuroimage 2012[2] Jenkinson et al., Neuroimage 2002[3] http://www.nitrc.org/projects/noddi_toolbox[4] http://www.trackvis.org

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MACHINE LEARNING TECHNIQUES IMPLEMENTED ON STRUCTURAL MR IMAGES TO DETECT GENDER-RELATED BRAIN ABNORMALITIES IN CHILDREN WITH AUTISM SPECTRUM DISORDER

A. Giuliano1, A. Retico2, S. Calderoni3, L. Biagi3, A. Cosenza3, R. Tancredi3, F. Muratori4, M. Tosetti3

1Dipartimento di Fisica, Università di Pisa, Pisa, Italy2Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, Pisa, Italy3IRCCS Fondazione Stella Maris, Pisa, Italy4Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Pisa, Italy

Introduction: The use of machine learning techniques is taking place as alternative method to standard univariate analyses.We employed support vector machines (SVM) to detect structural brain alterations of children with autism spectrum disorder(ASD) and to evaluate whether the brain abnormalities exhibit gender-related morphometric differences.Methods: The structural MRI scans of 152 children (2-7 years, 76 ASD matched to 76 control subjects for age, gender andnon-verbal IQ) were evaluated by SVM classification of the gray matter (GM) segmented with the SPM8 preprocessingalgorithm, based on the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure. Theleave-pair-out cross-validation protocol has been adopted to determine the classifier performance. The recursive featureelimination (RFE) procedure has been implemented to localize the most discriminant voxels contributing to sample sepa-ration. Group comparisons were performed both on all data (38 male + 38 female ASD children and their matched controls)and in male and female subsets.Results: SVMs correctly discriminate ASD male and female individuals with respect to controls with an area under the ROCcurve (AUC) above the 87% with a fraction of retained voxels in the 0.4-29% range. By choosing as operative point ofthe system that corresponding to the lower amount of significant voxels (0.4% of the total number of voxel) we obtained asensitivity of 0.82 and a specificity of 0.80. The discrimination maps obtained at that operative point showed the followingmain significant regions with an excess of GM in ASD subjects: Left (L) and Right (R) Superior Frontal Gyri (BA 10); Land R Precunei (BA 31); R Temporo-Parietal Junction (BA 39); L Superior Temporal Gyrus (BA 22); R Superior TemporalGyrus (BA 41). The separate analysis of male and female subgroups revealed that: L and R Precunei dominate the maleASD group; L and R Superior Frontal Gyri and Middle Frontal Gyrus characterize females.Conclusions: The multivariate SVM approach contribute not only to distinguish ASD from controls, but also to disentanglethe gender specificity of ASD brain alterations that could be related to sex-based differences in the phenotypic expressionof ASD.

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SEGMENTAZIONE DI GLIOMI IN IMMAGINI FLAIR BASATA SU ANALISI TOPOLOGICA DEI DATI

M. Rucco1, A. Castellano2, M. Donativi4, G. De Nunzio4, G. Pastore3, E. Merelli1, D. Herman7, T. Petrossian7, L. Bello5, A.

Falini2

1Univ. di Camerino, School of Science and Technology, Computer Science Division, Camerino2U.O. Neuroradiologia, Ospedale San Raffaele e Univ. Vita-Salute, Milano3Istituto di Ricerche Cliniche Ecomedica, Centro di Radioterapia e IGRT, Empoli4Dip. di Matematica e Fisica “Ennio De Giorgi”, Univ. del Salento, Lecce5U.O. Neurochirurgia, Ist. Clinico Humanitas, Univ. di Milano, Milano6Advanced Data Analysis in Medicine, http://adamgroup.it7Ayasdi Inc., Palo Alto - California

FINALITA'.La necessitá di sviluppare tecniche innovative per l’analisi di big data è stata in parte soddisfatta con lo sviluppodi algoritmi che trovano origine nella topologia algebrica e forniscono una rappresentazione compatta dei dati in input, eenfatizzando correlazioni che metodi statistici classici offuscherebbero. In questo studio abbiamo applicato alla segmenta-zione di gliomi in immagini FLAIR, l’algoritmo ”Mapper”[1], implementato nel software Iris, che fornisce la rappresentazionedel dataset di input in forma di un grafo costituito da nodi (cluster). La rappresentazione a grafo è ottenuta proiettando lecoordinate dei pixel in uno spazio metrico, i cluster sono collegati fra loro per similaritá di toni di grigio. I cluster statistica-mente significativi sono raggruppati in strutture ad “Y”o circolari.MATERIALI E METODI. L’analisi è stata effettuata su un ristretto numero di pazienti con gliomi sono stati sottoposti a RMa 3T con sequenze 3D-FLAIR volumetriche Lo spazio metrico adottato è quello di Hamming, che è risultato in grado diindividuare cluster statisticamente significativi sia in pazienti con gliomi sia omogenei, sia disomogenei. Per ogni pazientesono state estratte 4 slice dal volume patologico: 2 corrispondenti alle regioni superiore e inferiore del tumore, e 2 centrali.RISULTATI. Per ogni slice analizzata sono stati selezionati i pixel che costituivano i cluster individuati da Iris. I sottinsiemidi pixel sono stati proiettati sulle immagini originali tracciando delle ROI, poi confrontate con quelle prodotte dal medico.La qualitá del sistema di segmentazione è stata valutata con il coefficiente di Jaccard (JC). I risultati sono incoraggianti(valore medio di JC pari a 0.78) migliorabili eliminando i pochi falsi positivi presenti, con tecniche di morfologia matematicao con metodiche a soglia.CONCLUSIONI. Questo approccio, basato esclusivamente su toni di grigio si propone come nuovo strumento per la seg-mentazioni di immagini Flair. È in atto una sua validazione su 20 pazienti e sará testato su altre tipologie di immaginidiagnostiche e su un set piú ampio di feature.[1] Singh, Gurjeet, Facundo Mémoli, and Gunnar E. Carlsson. "Topological Methods for the Analysis of High DimensionalData Sets and 3D Object Recognition." SPBG. 2007.

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COMPUTER ASSISTED DETECTION IN NEUROIMMAGINI FLAIR E DTI: INDIVIDUAZIONE, SEGMENTAZIONEAUTOMATICA E VOLUMETRIA DEI GLIOMI CEREBRALI

M. Donativi1, A. Castellano2, G. De Nunzio1, G. Pastore5, M. Rucco3, A. Iadanza6, M. Riva4, L. Bello4, A. Falini 6

1Dip. di Matematica e Fisica “Ennio De Giorgi”, Univ. del Salento, Lecce e Advanced Data Analysis in Medicine2U.O. Neuroradiologia, Ospedale San Raffaele e Univ. Vita-Salute, Milano e Advanced Data Analysis in Medicine3Univ. di Camerino, School of Science and Technology, Computer Science Division, Camerino e Advanced Data Analysisin Medicine4U.O. Neurochirurgia, Ist. Clinico Humanitas, Univ. di Milano, Milano5Advanced Data Analysis in Medicine, http://adamgroup.it6U.O. Neuroradiologia, Ospedale San Raffaele e Univ. Vita-Salute, Milano

FINALITA'. I sistemi automatici (CAD, Computer Assisted Detection) per la segmentazione e la volumetria dei gliomi cere-brali sono di grande interesse per la valutazione dell’estensione tumorale nella diagnosi, la pianificazione terapeutica e ilfollow-up: l’uso di un CAD può ridurre la soggettività della diagnosi, aumentandone l’accuratezza.In questo studio le immagini FLAIR e DTI di pazienti con glioma cerebrale sono state elaborate tramite analisi statisticatessiturale 3D per caratterizzare la struttura del tessuto tumorale e sviluppare un tool di segmentazione supervisionataautomatica (“GlioCAD”), che fornisca la misura volumetrica delle lesioni e una valutazione degli istogrammi dei livelli digrigio di regioni di interesse [1].MATERIALI E METODI. 34 pazienti con gliomi di basso e alto grado sono stati sottoposti a RM a 3T con sequenze 3D-FLAIR

assiali e DTI (single-shot EPI, b=1000 s/mm2, 32 direzioni). Dalle immagini DTI sono state ottenute le mappe FA, MD, p eq. In ogni mappa sono state segmentate manualmente le regioni patologiche e, a queste ed al tessuto sano controlaterale,è stata applicata l’analisi tessiturale per identificare le caratteristiche (feature) discriminanti. La dimensionalità dello spaziodelle feature è stata ridotta tramite Linear Discriminant Analysis (LDA), permettendo la classificazione e la segmentazioneautomatica del tumore.RISULTATI. Per ogni mappa sono state calcolate sensibilità, specificità e curve ROC, con ottimi risultati (AUC=(0.90-0.97)).Per la fruizione in remoto di GlioCAD è stato realizzato un plugin per OsiriX, che permette caricamento e visualizzazionedelle immagini da segmentare, e l’invio al server sul quale risiede GlioCAD. Dopo un tempo di calcolo compatibile con lapratica clinica, le segmentazioni tornano al client e sono visualizzate insieme alle misure volumetriche e agli istogrammi.CONCLUSIONI. GlioCAD si propone come nuovo strumento, basato sull’analisi statistica tessiturale, per la segmentazioneautomatica dei gliomi cerebrali, la volumetria, e l’analisi quantitativa degli istogrammi nelle regioni di interesse.[1] G. De Nunzio, G. Pastore, M. Donativi, A. Castellano, A. Falini, A CAD system for cerebral gliomas based on texturefeatures in DT-MR images, NIM A, doi:10.1016/j.nima.2010.12.086 (2011)

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FRAMEWORK TO INTEGRATE STRUCTURAL, FUNCTIONAL AND METABOLIC MR IMAGES FOR SURGERY ANDRADIOTHERAPY PLANNING OF BRAIN TUMORS

R. Tarducci 1, A.M. Didona1, A.C. Dipilato2, M. Iacco1, M. Marcantonini1, C. Zucchetti1, P. Chiarini3, P. Floridi3, G. Gobbi1

1SC di Fisica Sanitaria - Azienda Ospedaliero Universitaria di Perugia2Sez. di Radioterapia Oncologica - Azienda Ospedaliero Universitaria di Perugia3SC di Neuroradiologia - Azienda Ospedaliero Universitaria di Perugia

AIMSThe surgical removal of brain tumors is a critical operation, as it may lead to functional impairment, but also to recurrentsurgery if a tumor is not completely removed. Therefore, good surgical planning is crucial to minimize damage to importantfunctional areas.The aim of this work is to develope a framework to display, in an integrate view, images with structural informations, i.e.standard magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI), functional information (fMRI) and metabolicinformation (3D 1HMRS).MATERIALS AND METHODSAll data were acquired using 3 T Philips MR tomography with Invivo device for fMRI acquisition. We acquired: standardmagnetic resonance imaging, 32 directions diffusion tensor imaging, fMRI to localize critical area (motor area, languagearea, ...), 3D 1H spectroscopic imaging to identify abnormal coline (Cho) or lactate (Lac) concentration. The data wereprocessed using several software, Statistical Parametric Mapping (SPM, www.fil.ion.ucl.ac.uk), FSL (FMRIB Software Li-brary, fsl.fmrib.ox.ac.uk), MedINRIA (Institut National de Recherche en Informatique et en Automatique, www.inria.fr).RESULTS AND CONCLUSIONAfter creation process, the datasets are coregistred using transformation matrices defined from original images series andall datasets are transcribed in DICOM. The coregistration of the MRSI data in MRI/DTI/fMRI datasets is a bit more compli-cated. After the generation of color maps based on Cho and Lac concentrations, the processing software create the 3D VOI.This volume is converted to DICOM format and the DICOM tags of slices localizzation, extracted from acquisition process,it is inserted. The computations are made using home made software based on Octave (www.gnu.org/software/octave).All datasets coregistred and in DICOM format was ready to use for surgery or radiotherapy planning systems.Several autors have described the utility of combining fMRI and DTI for surgery planning but, particularly for radiotherapy,also MRSI dateset is important (1).(1) Pattern Recognition of MRSI Data Shows Regions of Glioma Growth That Agree With DTI Markers of Brain TumorInfiltration; Magnetic Resonance in Medicine 62:1646–1651 (2009)

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Early Perfusion Changes in Patients with Recurrent High-Grade Brain Tumor Treated with Bevacizumab: aPreliminary Evaluation by the Parametric Response Map derived from Dynamic Contrast-Enhanced MRI

S. Marzi1, F. Piludu2, V. Villani3, A. Pace3, A. Fabi4, C.M. Carapella5, A. Vidiri2

1Medical Physics Laboratory, Regina Elena Cancer Institute, Rome, Italy2Radiology and Diagnostic Imaging Department, Regina Elena Cancer Institute, Rome, Italy3Neurology Division, Regina Elena Cancer Institute, Rome, Italy4Oncology Department, Regina Elena Cancer Institute, Rome, Italy5Oncologic Surgery Department, Regina Elena Cancer Institute, Rome, Italy

Objective: to determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas,by the Parametric Response Map derived from Dynamic Contrast-Enhanced MRI (DCE-MRI), may be a predictor of theresponse to treatment assessed through conventional MRI follow-up.Methods: 20 patients will be enrolled in the present study. For each patient, two DCE-MRI examinations, before and afterthe first dose of bevacizumab, will be acquired. The region of interest will be defined on the IAUGC (Initial Area UnderGadolinium Concentration) maps, using co-registered T1-weighted contrast-enhanced images as a guide to the tumorlocation. For both perfusion parameters, the parametric response map (PRM) (1) will be calculated. The PRM is a voxel-wiseanalysis method that allow to identify and quantify the regions wherein the parameter value increased, decreased or wasstable during or after a therapy. The modifications of hyper and hypo-perfused sub-volumes, including tumor necrosis, willbe assessed within the lesion using a volumetric histogram analysis. The significance of changes in the different perfusionmetrics, observed at baseline and during treatment will be established. The relationships between changes in perfusionand morphological MRI modifications at first follow-up will be investigated.Results: Preliminary results on eight patients showed significant reductions in both IAUGC and Ktrans values after onlya single dose of bevacizumab. Both the PRMs and the histogram modifications indicated the normalization effect of beva-cizumab on the tumor abnormal vasculature. An improvement in hypoxia after a single dose of bevacizumab seems tobe predictive of a greater reduction in T1-weighted contrast-enhanced volumes at first follow-up and a better responseto treatment.Conclusions: A quantitative image approach, based on the volumetric histogram analysis and the PRM may provide usefulinformation to early demonstrate local effect of the anti-angiogenic agent.References:(1)Galbán CJ et al. Prospective analysis of parametric response map-derived MRI biomarkers: identification of earlyand distinct glioma response patterns not predicted by standard radiographic assessment.Clin Cancer Res. 2011 Jul15;17(14):4751-60.

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Differences in DSC-MR perfusion maps generated by different commercial software

L. Orsingher1, G. Crisi2, S. Piccinini1

1Parma University Hospital Trust; Parma, Italy, University of Sacro Cuore - Rome2Parma University Hospital Trust; Parma, Italy

Purpose: To investigate the variability in the quantitative estimates of DSC-MRI parameters [1] obtained from a cohort ofpatients with glioblastoma multiforme (GBM) by using two commercially available software with different post-processingalgorithms.Methods and materials: We retrospectively evaluated DSC-MRI datasets of 24 consecutive patients with glioblatoma mul-tiforme (GBM). All MR imaging and DSC-MRI scans were performed on a 3T whole-body scanner (GE Healthcare, USA)equipped with an 8 channel phased-array head coil. Perfusion data were postprocessed with two commercial softwarepackages, NordicICE (NordicNeuroLab, EU) and GE Brainstat (GE Healthcare, USA), each of which offer the possibility of

different algorithms. We focused the comparison on their main characterizing points, i.e. the use or not of Γ-variate fittingfunction and of the arterial input function (AIF). Two ROIs were placed on the perfusion parameters (CBV,CBF,MTT) maps:one around tumor hot spot and one in the contralateral normal brain. A one-way repeated- measures analysis ANOVA hasbeen conducted to determine whether there was a significant difference in the calculated MTT, CBV and CBF values.Results: As regards NordicICE software package, the use of AIF is significant (p=0.048) but not the use of gamma-variate(p=0.803) as the calculation method for CBV. On the other hand, in the framework of GE, there was no statistical differences

between the algorithm with AIF and without Γ-variate fitting and the one with Γ-variate fitting and without AIF. Comparingsimilar GE-NordicICE algorithms, both method (p=0.005) and software (p<0.0001) have a statistical effect in the difference.As regards “institutional” units, the group of methods with gamma and without AIF do not present statistical differences inCBV values distribution while statistical differences exist among methods with AIF.Conclusion: Statistical differences have been detected both between and within different vendor software. The sources ofdifferences are different between software. Institutional units have shown interesting characteristics.References:[1] Kiselev VG, On the theoretical basis of perfusion measurements by dynamic susceptibility contrast MRI, Magn ResonMed 2001, 46:1113-22

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QUANTITATIVE ANALYSIS AT 1.5T MUSCLE MRI in NEUROMUSCULAR DISORDERS

M.E. Fantacci1, G. Astrea2, R. Battini2, A. Retico3, C. Sottocornola1, M. Tosetti2

1Dipartimento di Fisica dell'Università di Pisa e INFN Sezione di Pisa2IRCCS Fondazione Stella Maris, Calambrone, Pisa3INFN Sezione di Pisa

Magnetic Resonance Imaging (MRI) is a reliable and non invasive tool for clinical assessment and follow up in neuromu-scular disorders (NMD). We describe an analysis method to develop a quantitative evaluation of the fat infiltration and torelate it to the grade of muscle impairment.Images of 10 healthy subjects and of 16 various (limb girdle diseases, congenital myopathies) NMD patients have beenanalyzed. All data were acquired at IRCCS Stella Maris with a 1.5T scanner MR Signa GE Medical Systems HDxT with awhole body TX-RX coil. The protocol [1] consisted of a 2D axial T1-weighted Spin Echo sequence with matrix of 256×256,FOV=44cm×44cm, TE=14ms and TR=540ms. The analysis system has been developed and implemented as an originalhierarchical module network in the MeVisLab analysis framework. The system comprises algorithms for automatic seg-mentation and for characterization, in geometry and signal intensities, of the muscle and fat segmented regions in healthysubjects, and for quantification of fat infiltration percentage in patients muscles. 8 patients scans have been selected, blin-ded to the automatic analysis findings, to form a gold standard for 4 grades of effective muscle involvement as evaluatedduring conventional neuromuscular assessment; the other 8 patients scans have been used to validate the method.In healthy subjects the voxel intensities of fat and muscle tissues resulted distributed as gaussian functions with a constantratio of their mean values (3.4±0.3), and the percentage of non-muscular voxels in the muscular segmented area is lowerthan 7%. In NMD patients only the voxel intensities of fat are distributed as a gaussian function, whose mean corresponds tothat of healthy subjects. The quantitative automatic evaluation of fat infiltration percentage for the 8 patients of the validationset, ranging between 4.7% and 96.9%, has been related to the grade of muscle involvement. In all cases the classificationobtained by the automatic analysis system resulted the correct one.The quantitative analysis of muscle MRI resulted a promising instrument also to increase the characterization of patternsof fat infiltration in neuromuscular patients. An increase of the dataset is still ongoing.[1]Mercuri E et al, J Magn Res Im 25, 433-40, 2007.

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Realistic Estimation of the Local Specific Absorption Rate of Human Calf in MR Scanner at 7T

G. Tiberi1, M. Costagli1, R. Stara2, N. Fontana3, A. Retico4, L. Biagi5, A. Monorchio3, M. Cosottini6, M. Tosetti5

1Fondazione Imago7, Pisa, Italy2Dipartimento di Fisica, Universita' di Pisa, Italy3Dipartimento di Ingegneria dell'Informazione, Universita' di Pisa, Italy4Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, Italy5IRCCS Stella Maris, Pisa, Italy6Dipartimento di Radiologia Diagnostica e Interventistica, Universita' di Pisa, Italy

The evaluation of the local Specific Absorption Rate (SAR) is a major concern in ultra-high field (UHF) MR systems. Theinvestigation here presented is focused on the estimation of the SAR in human calf excited by a 7T surface coil. The aim ofour work is to evaluate the maximum local SAR of the sample inside the scanner under realistic condition of use. We derivethe distribution of the local SAR by the combination of numerical electromagnetic simulation (CST MW Suite) and MRacquisition obtained at the GE MR950 7T human system (GE HealthCare, Milwaukee, WI, USA) at Imago 7 Foundation,Italy.The test case used for the proposed approach is the human calf excited by a home-built RF MR dual tuned surface coil.The RF coil has been tuned and matched in order to resonate at the 1H and 31P Larmor's frequencies at 7T, i.e. at 298MHzand 120MHz respectively. However, for the present investigation, we focused our attention on 1H only.Transmitted B1+field was measured on a volunteer adult calf by employing the Bloch-Siegert Shift (BSS) method. The input power of 1Hchannel has been manually set to 0.04 KW. CST MW Suite was used to model both the coil and the calf. Specifically,simulations for evaluation the electromagnetic fields have been conducted using a numerical heterogeneous human calf ofthe 1x1x1 mm3 HUGO voxel model, having the dielectric properties of tissues. The HUGO model has been appropriatelyscaled to match the size of the volunteer adult calf.For evaluating the SAR under realistic condition of use we compared the simulated B1+ and the measured B1+ on thetransversal plane and we performed an appropriate power scaling in the simulations.The maximum local SAR for unit RF cycle was 11 W/Kg. We can conclude that the simulation software, in conjunctionwith measured B1+ maps, is suitable for producing maps of local SAR that can be used for assessing safety in UHF MR.Obviously, in order to give an estimation during the complete MR exam and to demonstrate the compliance with the requi-rements, the averaging time equal to 6 min has to be applied. Specifically, since the SAR depends on the characteristicsof the sequence adopted during the MR exposure, all the parameters related to the sequence itself have to be taken intoaccount in the calculation.

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Safety Protocol for monitoring side-effects at the first Italian 7T MRI facility

I. Pesaresi1, D. Frosini2, L. Biagi3, M. Costagli4, G. Tiberi4, R. Stara5, M. Tosetti3, M. Cosottini2

1UO Neuroradiology, Santa Chiara Hospital, Pisa, Italy2Department of Neuroscience, University of Pisa, Italy3Fondazione Stella Maris, Pisa, Italy4Fondazione Imago7, Pisa, Italy5Department of Physics, University of Pisa, Italy

Introduction.Over 100 experiments on human adults performed at Imago7 Foundation have been used to adopt a "Safety Protocol"that monitors objective as well as subjective side-effects at 7T. Specifically, we report and analyze in a quantitative andqualitative manner the data obtained from questionnaire on tolerability/side-effects raised during the exams on a sampleof volunteers. All data were collected at the Imago7 Foundation and have been authorized for this study.Methods.The data have been collected during the exams on 101 subjects; exams were performed using a GE MR950 7T humansystem (GE HealthCare, Milwaukee, USA). Subjects include 62 males and 39 females, all aged between 19 and 74 years.Screening tolerability was conducted through a questionnaire after the exam. The collection of data for statistical purposeswas done by assigning a score for each item and generating a final score. Data have been divided in two groups, onerelated to the sliding of the couch into the magnet, and the other related to the acquisition period. The score for the twogroups of the experiment has been assigned as following:Group I - During "couch advancing". In this group there are 5 items (vertigo, nausea, metallic taste, phosphenes, electricsensation); we assign a value of 1 to the answer NO, and 0 to answer YES. In this group, the maximum of the score is5, which indicates maximum tolerability;Group II - "During the exam". In this group there are 10 items (pain, claustrophobia, palpitation, discomfort, troublesomenoise, vertigo, nausea, metallic taste, phosphenes, electric sensation); and is we assign a value of 1 to the answer NO,and 0 to answer YES. In this group, the maximum of the score is 10, which indicates maximum tolerability.Results.Fifty-five subjects (53%) reported at least one side effect, but all were mild in intensity and did not require exam interruption.Any serious adverse event was reported. Mean tolerability score for “couch advancing” was 4.57/5 and for the “exam”was 9.20/10.Conclusion.These preliminary data, yet on a relevant number of subjects, suggest that ultra high field MRI is practicable with safetyand is well tolerated without excessive discomfort to subjects. In particular, the discomfort reported by subjects is similarto that experienced at lower fields.

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From dream to reality: applying theoretical physics to in-vivo NMR

S. Nicolosi1, G. Russo1, G. Borasi1

1IBFM CNR - LATO, Cefalù, Palermo, Italia

The idea of implementing quantum devices based on the properties of single quantum particles has gone progressivelygrowing up in the course of the last few years. The reason can be envied in the high contemporary evolution of theore-tical dynamical models along with the ability reached by experimentalists in manipulating quantum objects first conside-red “theoricians' tools”. The state of art is that, although it has been possible to obtain the exact dynamical equations ofOpen Quantum Systems (including Nuclear Magnetic Resonance (NMR)) and these equations have been solved in highlysymmetrical systems, the inability to hypotize a microscopic interaction inside high anisotropy systems makes the solutionmerely formal [1]. Despite this, the decay of the populations and quantum coherence (modelled by the phenomenologicalBloch equations) is at the root of phenomena such as EPR and NMR has always been considered the major topics ofquantum mechanics.The theoretical foundations and the characteristics of the models and methods used in Nuclear Magnetic Resonance todescribe the properties of absorption and emission of an ensemble of spins are imposed and derived from purely quantumstochastic equations representing the equivalent of the phenomenological Bloch equations.This research work aims to participate in the open debate which aims to establish an interaction between the theory ofOpen Quantum Systems and in vivo NMR and includes a limited number of case studies.[1] Breuer and Petruccione, The Theory of open quantum systems, Oxford University Press, (2002); Abragam, Principleof Nuclear Magnetism, Int. Series of Monographs on Physics 32, Oxford University Press, (1961); C.P. Slichter, Principlesof Magnetic Resonance, Springer-Verlag, New York, Heidelberg, Berlin, (1990); S. Nicolosi, An Operator-Based exacttreatment of Open Quantum System, Open System and Inf. Dynamics, 12: 163-177 (2005)

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Magnetic Resonance guided Focused Ultrasound (MRgFUS) treatment of hepatic cancer: preliminary experiencein tumor control.

F. Sandolo1, M. Anzidei1, A. Napoli1, M. Del Monte1, F. Boni1, C. Catalano1

1Department of Radiological, Oncological and Pathological Science

PURPOSE:Hepatocellular carcinoma(HCC) represents one of the most challenging abdominal tumor, mostly due tothe peculiar anatomy of the involved organ, to vascular relationship and to the very poor response to conventionalchemotherapy.At present, percutaneous ablation techniques and transarterial embolization are feasible therapeutic optionsfor HCC, having surgery strict inclusion criteria.Hepatic lesions have been successfully treated with focused ultrasound under conventional US guidance; a non-invasiveablative technique with the possibility to be repeated if necessary with very limited possible complications.MR guidedfocused ultrasound ablation (MRgFUS) introduces the advantage of real time monitoring, allowing a more precise ablationof the lesion and a more accurate in-treatment patient management.Therefore our purpose is to evaluate the feasibility ofMRgFUS ablation in selected hepatic primary tumors.MATERIALS AND METHOD:1 patient with unresectable HCC (female; 62yr) underwent MRgFUS on a dedicated 3Tunit featuring the ExAblate2100 system (InSightec). The treatment was performed in general anesthesia with breathcontrol.After the procedure, gadolinium-enhanced GRE-T1W sequences were performed to evaluate the ablated area andthe absence of possible local complications.Clinical and imaging follow-up was performed with both MR and CT at 3 and6 months after treatment.RESULTS:Treatment was successfully performed without any adverse events during or after the procedure.MR imagesacquired immediately after treatment demonstrated necrosis of ablated area within the lesion without lesion-enhancing.Atshort term (1-3 months) imaging follow-up showed progressive shrinkage of the ablated area without residual viable tumor.At 1yr follow-up, CT showed a satellite sub-centimetric lesion consistent with perilesional recurrence. At 18 months postMRgFUS patient underwent liver transplant and histology confirmed the area of post-ablative fibrosis with the satellitenodular lesion.CONCLUSIONS:Our preliminary clinical experience suggests that MRgFUS is a feasible ablative technique in patients withunresectable(or not suitable for surgery) and device-accessible hepatic lesions.

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HIGH INTENSITY FOCUSED ULTRASOUND ABLATION OF PANCREATIC CANCER: A TOTALLY NON-INVASIVETREATMENT FOR TUMOR CONTROL OF LOCALLY ADVANCED LESIONS (STAGE III)

F. Zaccagna1, A. Napoli1, M. Anzidei1, M. Del Monte1, V. Noce1, C. Catalano1

1Department of Radiological, Oncological and Pathological Sciences - Sapienza University of Rome

Purpose: Pancreatic cancer is a common malignant neoplasm of pancreas with an increasing incidence, a low early dia-gnostic rate and a fairly poor prognosis. To date, the only curative therapy for pancreatic cancer is surgical resection, butonly about 20% patients have this option at the time of diagnosis and the mean 5-year survival rate after resection is only10%-25%. Furthermore, pancreatic cancer is highly chemotherapy-resistant and has one of the highest fatality rates of allcancers and is the fourth highest cancer killer worldwide. MR guided focused Ultrasound (MRgFUS) has recently beenproposed as a new non-invasive treatment for ablation of different solid tumors, such as pancreatic cancer. On the basisof this knowledge our purpose was to evaluate safety and effectiveness of non-invasive high intensity MRgFUS treatmentfor tumor control of locally advanced pancreatic cancer.Materials & methods: 5 patients with locally advanced pancreatic cancer underwent focal ablation with MRgFUS treatmentusing the ExAblate 2100 system (InSightec). Treatments were done in a single session, in an ambulatory setting. Toevaluate tumor control, perfusion T1w-images after administration of gadobenate dimeglumine (MultiHance; Bracco, Milan,Italy) were obtained pre- and post-treatment in order to determine the non-perfused sonication-related area. Follow-upexaminations were scheduled at 1, 3, 6 and 12 months after treatment. After treatment all patients underwent CHT withthe same chemotherapy scheme.Results: All patients well tolerated the treatment and no heating related adverse event were recorded during this clinicalapplication. Immediately after treatment all patients showed coagulative necrosis with a mean non perfused volume of65.4±16.6 [45 - 90]. All patients showed a significative decrease of pain due to cancer infiltration.At follow-up tumor recurrence in treatment site was MRI evident but no local progression were recorded. After MRgFUS 2patients underwent RT meanwhile one patients required another MRgFUS treatment.Conclusion: Our preliminary clinical experience indicates that focused ultrasound under MR guidance could be a promisingnoninvasive treatment modality to obtain a reduction of tumor size in patients with pancreatic adenocarcinoma not suitablefor surgery.Bibliography: Clinical and future applications of high intensity focused ultrasound in cancer. Al-Bataineh O, Jenne J, HuberP. Cancer Treat Rev. 2012 Aug;38(5):346-53

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Ultra-high b-value diffusion-weighted imaging for the detection of prostate cancer with 3-T MRI

D. Fierro1, F. Barchetti1, V. Forte1, M.G. Bernieri1, C. Catalano1, V. Panebianco1

1Dip Radiol Sapienza University of Rome

OBJECTIVES: To compare diffusion-weighted imaging (DWI) efficacy at 3T MR using ultra high b value (3000 s/mm2)obtained with both endorectal and phased-array coils (ERC + PAC) to DWI acquired with only an PAC for assessingprostate cancer (PCa).MATERIALS AND METHODS: Fifty patients with biopsy-proven prostate cancer underwent preoperative 3T MRI usingT2-weighted imaging (T2WI) and DWI (b = 0, 500, 1000, 3000 s/mm2) with two different coil arrangements: ERC + PAC(protocol A) and PAC only (protocol B) in the same session. Two radiologists evaluated separately T2WI and DWI imagesobtained with ERC + PAC and PAC only. Histopathological findings of radical prostatectomy were used to validate MRIresults. For diagnostic capability estimation, area under the receiver operating characteristic (ROC) curve (AUC) was cal-culated. On b = 0 images, signal-to-noise ratios (SNRs) were measured as the ratio of the mean signal from PZ and TZROIs to the standard deviation from the mean signal in an artifact-free ROI in the rectum. For each ROIs, mean ADC valuesfor all zero and non-zero b-value combinations were computed.RESULTS: ERC + PAC T2WI and DWI show 98 % sensitivity, 94 % specificity and 93 % accuracy in identifying PCa whilePAC only display 97 % sensitivity, 95 % specificity and 92 % accuracy. Reader 1 rated AUCs as 0.66 in protocol A and0.77 in protocol B; reader 2 rated AUCs as 0.70 in protocol A and 0.81 in protocol B. Mean SNR with ERC-MRI at PZ(65.36 ± 23.05) and TZ (34.75 ± 11.27) was 10.17 and 6.49 times higher than with PAC-MRI (6.42 ± 3.13 and 5.35 ±1.69), respectively, (P < 0.0001 for both). ADCs from DW-MR images obtained with all b-values in the PZ and TZ weresignificantly lower with PAC-MRI than with ERC-MRI (P < 0.001 for all).CONCLUSION: Use of ultra high b value (3000 s/mm2) for DWI with 3-T MRI is diagnostically superior in PCa detectionwith both ERC+PAC then PAC only. The use of ERC+PAC improves prostate imaging by providing greater signal-to-noiseratio (SNR) and therefore increases spatial resolution.

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Non-invasive focal therapy of organ confined prostate cancer: Phase I study using Magnetic Resonance guidedFocused Ultrasound technology and excision pathology for efficacy assessment

P.L. Di Paolo1, A. Napoli1, G. Cartocci1, F. Zaccagna1, M. Del Monte1, F. Boni1, L. Bertaccini1, V. Panebianco1, C. Catalano1

1Dipartimento Scienze Radiologiche, Oncologiche e Anatomo Patologiche. Università di Roma La Sapienza

Purpose. To assess safety and initial effectiveness of non-invasive high intensity 3T MR guided focused Ultrasound (MRg-FUS) treatment of localized prostate cancer in a phase I, treat and resection designed exploratory study.Materials and Methods. On the basis of a power analysis, 11 patients with biopsy proven focal T2 prostate cancer (low-to-intermediate risk: PSA max 12 and Gleason max 3+4), confirmed on a previous multiparametric MR exam (Discovery 750,GE) including dynamic contrast enhanced (DCE) imaging (Gd-BOPTA, Bracco), underwent MRgFUS ablation (ExAblate,InSightec). All patients were scheduled to radical laparoscopic prostatectomy; MRgFUS treatment was carried out on theMR identifiable lesion (max 2) using a patient specific energy (3000-8500 J) and real time MR thermometry monitor forcorrect treatment location. Non-perfused volume (VPV) in the post-ablative MRI was than compared with excision pathologyfor necrosis assessment.Results. No significant complications were observed in all subjects during or immediately after the procedure. Procedurewas validated by pathologist, that demonstrated extensive coagulative necrosis at the site of sonication surrounded bynormal prostatic tissue with inflammatory changes; these features positively compared with immediate post-ablative MRIscan and NPV. At histology 10 patients were free of residual viable tumor within the treated area; in the remaining patient,10% of residual tumor was observed within the NPV. There was a variable amount of isolated cancer tissue (Gleason max6, 3+3) within the non-treated parenchyma that was neither identifiable at MRI nor at biopsy.Conclusion. Results of our Phase I study suggest MR guided Focused Ultrasound as a safe and effective modality todetermine >90% necrosis of identifiable prostate cancer; other prospective studies are needed to extend success rate inlarger cohort.

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In vivo 3D neuroanatomical evaluation of periprostatic nerve plexus with 3T-MR Diffusion Tensor Imaging.

F. Barchetti1, V. Forte1, M.G. Bernieri1, C. Catalano 1, V. Panebianco 1

1Dip. Radiol. Policlinico Umberto I Sapienza Università di Roma

OBJECTIVES: To evaluate if Diffusion Tensor Imaging technique (DTI) can improve the visualization of periprostatic ner-ve fibers describing the location and distribution of entire neurovascular plexus around the prostate in patients who arecandidates for prostatectomy.MATERIALS AND METHODS: Magnetic Resonance Imaging (MRI), including a 2D T2-weighted FSE sequence in 3 planes,3D T2-weighted and DTI using 16 gradient directions and b=0 and 1000, was performed on 36 patients. Three out of 36patients were excluded from the analysis due to poor image quality (blurring N=2, artifact N=1). The study was approved bylocal ethics committee and all patients gave an informed consent. Images were evaluated by two radiologists with differentexperience in MRI. DTI images were analyzed qualitatively using dedicated software. Also 2D and 3D T2 images wereindependently considered.RESULTS: 3D-DTI allowed description of the entire plexus of the periprostatic nerve fibers in all directions, while 2D and3D T2 morphological sequences depicted part of the fibers, in a plane by plane analysis of fiber courses. DTI demonstratedin all patients the dispersion of nerve fibers around the prostate on both sides including the significant percentage presentin the anterior and anterolateral sectors.CONCLUSIONS: DTI offers optimal representation of the widely distributed periprostatic plexus. If validated, it may helpguide nerve-sparing radical prostatectomy

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A PRELIMINARY DTI STUDY OF MUSCLE ARCHITECTURE IN OSTEOPOROTIC AND OSTEOARTHRITICSUBJECTS

G. Di Pietro1, M. Palombo2, J. Baldi4, E. Piccirilli4, M. Celi4, U. Tarantino4, S. Capuani3

1Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia,Viale Regina Elena 291, 00161,Rome, taly2Physics Department, “Sapienza” University of Rome, Italy3CNR IPCF UOS Roma, Physics Department, “Sapienza” University of Rome, Italy4Department of Orthopaedics and Traumatology, University of Rome “Tor Vergata”, Rome, Italy

Osteoporosis and osteoarthritis are the most common diseases of musculoskeletal system1. A recent study showed that in

osteoporotic subjects (OP) a preferential type II fibers atrophy occurs compared to osteoarthritic patients (OA)2. This studyinvestigates, in vitro at 9.4T, the microstructural features in vastus lateralis muscles (VL) of OP and OA using diffusion

tensor imaging (DTI)3.VL biopsy was performed, after obtained written informed consent, in eight OP and in twelve OA. Each muscle of 2 cm wasstored in a 4% paraformaldeyde and PBS. DTI protocol consists of Pulsed Field Gradient Stimulated Echo sequence (b-

values=400-700s/mm2, TE/TR=14.5/2500ms, D/δ=40/2 ms, FOV=0.75 cm, number of average 4, twelve axial slices, STH=

1 mm). We evaluated FA, MD and the three eigenvalues (λ1>λ2>λ3) ) in each slice. Mean + SD values were obtained foreach variable. Muscle fibers of 4 OP and 6 OA were counted and classify using ATP-ase immunohistochemistry reactionand fiber diameter (FD) was obtained. Differences between groups and between pairs of variables were assessed byStudent’s t test and linear correlation analysis, respectively.

MD,λ1,λ2 and λ3 were significantly lower in OP compared to OA. This issue confirms the supposed association between

OP and sarcopenia4. Recently observations5 suggest a reduction of muscle mass corresponding to an increase of adiposetissue infiltration. According to this finding we found that OP muscles have higher fat infiltrations compared to OA muscles.These infiltrations could cause a restricted diffusion inside muscle fiber resulting in a smaller MD and in a reduction of the

three eigenvalues. In OP subjects a significant positive linear correlation was found between MD,λ2, λ3 and type II FD. This

finding confirms previous histological evidences2 about the prevalence of type II fiber atrophy in OP patients.In conclusion this analysis shows that DTI measurement is a powerful tool to detect differences in the muscle structuredue to different musculoskeletal pathologies.

References.1Baohua LI et al. J. Bone Miner. Res. 1997,12.4:641-651. 2Tarantino U et al. 2012,7:S141-S151. 3Basser PJ

NMR Biomed. 1995,8:333-344. 4Di Monaco M. et al. Arch. Gerontol. Geriat. 2011,52:71-74. 5Song MY et al. Am. J. Clin.Nutr. 2004, 79:874-880

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MRI OF HUMAN CALF AT 7 T

M.E. Fantacci1, G. Astrea2, R. Battini2, M. Costagli 3, C. Sottocornola1, M. Tosetti2

1Dipartimento di Fisica dell'Università di Pisa e INFN Sezione di Pisa2IRCCS Fondazione Stella Maris, Calambrone, Pisa3Fondazione IMAGO7, Calambrone, Pisa

There is increasing evidence that magnetic resonance imaging (MRI) of the muscle can be a valuable additional tool todiagnose inherited NeuroMuscular Disorders (NMD) by allowing the identification of patterns of muscle involvement. Newultra-high field (UHF) 7T MRI systems, with their greater signal-to-noise ratio (SNR), may offer increased quality and spatialresolution as well as shorter scanning time compared to lower field systems [1]. Here we describe the optimization of animage acquisition protocol at 7 T, aiming at discriminating muscle and fat in the human calf to evaluate fat infiltrations.Acquisitions were performed on a MR950 7 T human research MRI system equipped with a 2-channel transmit/receivebirdcage coil. The optimization of sequence parameters and the characterization of muscle and fat tissues (T1, T2 andT2*) were first performed on ex-vivo samples. A wide variety of sequences based on Spin Echo (SE), Inversion RecoverySE and Gradient Echo (GRE) were tested, including the spoiled gradient-recalled echo (SPGR) Dixon technique IDEAL-IQ [2], which exploits the chemical shift between water and fat. Sequences that were promising for preliminary human in-vivo muscle acquisitions at 7 T were selected and optimized on healthy volunteers.The sequences selected for inclusion in a new protocol for NMD human calf studies are a Fast Recovery Fast Spin Echo(FOV 15cm x 15cm, matrix size 512x512, TR 350 msec, nominal TE 15 msec, ETL 6, BW 83.33 kHz) and an IDEAL-IQ (FOV 15cm x 15cm, matrix size 512x512, TR 11 msec, TE 4.4 msec, FA 11º, BW 83.33 kHz). The images of healthyvolunteers acquired with these sequences at 7 T show a higher spatial resolution (0.293mm x 0.293mm) and a betterfat-muscle contrast (82±4 % and 87±4% respectively) with respect to those obtained at 1.5 T with the standard NMDprotocol [3] (1.72mm x 1.72 mm, 71±7% in SE). They constitute very promising preliminary results for precise muscle andfat discrimination and therefore for studying NMD muscle degeneration.[1] Regatte RR et al, J Magn Reson Imaging 2007; 25(2), 262-269.[2] Dixon WT. Simple proton spectroscopic imaging. Radiology 153:189-194, 1984.[3] Mercuri E et al, Eur J Paediatr Neurol 2002; 6: 305-307.

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NMR non-Gaussian diffusion experiments to investigate bone marrow

M. Palombo1, V. Di Marco1, S. Capuani 1

1Dip. di Fisica, "Sapienza" Università di Rome

Bone marrow is an heterogeneous complex system comprised of hematopoietic tissue islands and adipose cells surroundedby vascular sinuses. It is a soft tissue, mainly characterized by different relative percentage of water and fat rearranged in

spherical particles with average size ranging from 6 to 100 µm. The aim of the present study was to investigate the potentialof Gaussian and non-Gaussian diffusion NMR methods to obtain information about the microstructural complexity and thewater compartmentalization in two kind of bone marrow samples: free (not forced in pores of mammalian cancellous bone)and trabecular (filling the pores) bone marrow, by investigating water and fat effective diffusion coefficient, Deff, behavior as

a function of diffusion time, ∆. Our results suggest that: 1) molecular dynamics associated with fat protons is much slower(two order of magnitude) than that of water; 2) two distinct pool of diffusing water molecules, fast and slow, corresponding to

an extra and an intra cellular compartment exist; 3) in free bone marrow Deff(∆) of the fast extracellular water was found to

be constant, while the slow intracellular water exhibits decreasing Deff(∆) values as a function of ∆. Conversely, in trabecular

bone marrow Deff(∆) of both fast and slow water exhibit a decreasing trend as a function of ∆; 4) the extracellular fastdiffusing water in trabecular bone marrow exhibits strongly non-Gaussian dynamics.

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BREAST SILICONE IMPLANT MRI : PROTOCOL OPTIMIZATION AT 3T

I. Carne1, P. Caprotti2, L.G. Moro1, D. Fantinato1

1Servizio di Fisica Sanitaria, Fond. S. Maugeri Pavia2Servizio di Radiologia, Fond. S. Maugeri Pavia

Introduction -Most breast implant ruptures occur 10 to 15 years after implantation. The aim of imaging implant is to provide informationabout prosthesis integrity and abnormalities. Magnetic Resonance Imaging is the most sensitive and specific technique forthe detection of breast implant intracapsular and extracapsular ruptures.Materials and methods -Two phantoms made with single-lumen and double-lumen silicone gel prosthesis were enveloped with sliced bacon in orderto simulate adipose tissue and muscle around the silicone implant.Discovery MR750 3T scanner (GE Healthcare) was used. High field strength was preferred because the resonance fre-quency differences between silicone, fat and water allow to suppress/empathise signals. T1 and T2-weighted sequenceswere performed using a dedicated 8-channel breast coil.Results -A Fast Spin Echo T2-weighted sequence was optimized in order to get information from bilateral implants in the axial plane.This sequence provides water, fat, in-phase and out-phase images and such images in most cases permit a completeclinical evaluation of the implants (acquisition time = 4 min, slice thickness = 3.5 mm, TE = 92 ms, Matrix = 384x352).A 3D T1-weighted sequence was also optimized (acquisition time = 1 min 30 s, Matrix = 270x270) to study irregular andfolded profiles not easily detected with other imaging technique (i.e. ultrasonography). Bright and black silicone contrastsequences were optimized (IR fat suppression, chemical saturation for water/silicone signal, acquisition time = 5 min, slicethickness = 4 mm, Matrix = 320x256) for a single (left/right) prosthesis sagital view.Conclusions -The use of silicone-bacon phantoms allowed to optimize a protocol to study patients with prosthesis intracapsular shellfragments (with multiple low-signal intensity lines, the “linguine sign”) or extracapsular ruptures (with leakage of siliconeinto surrounding breast tissue), with a good compromise between spatial resolution and acquisition time.Bibliography -L. Everson, H. Parantainen, T. Detlie, A. Stillman, P.Olson, G.Olson, G.Landis, M. Foshager, B. Cunningam, H. Griffiths(1994) Diagnosis of Breast Implant Rupture : Imaging Finding and Relative Efficacies of Imaging Tecniques. AJR 1994;163:57-60.

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MAGNETIC RESONANCE IN MEDICINE FROM ADVANCED TECHNOLOGICAL RESEARCH TO CLINICALPRACTICE: THE QUEEN SQUARE EXPERIENCE (FROM A CLINICAL SCIENTIST PERSPECTIVE)

L. Mancini1, M.J. White1, E. De Vita1, C.D.J. Sinclair1, J.S. Thornton1, X. Golay1, T. Yousry1

1Lysholm Dept. of Neuro-radiology, National Hospital for Neurology and Neurosurgery, University College London HospitalsNHS Foundation Trust, London and Neuroradiological Academic Unit, Institute of Neurology, University College of London,London

Translating advanced magnetic resonance imaging (MRI) methods in clinical practice for diagnosis, treatment monitoring ortherapy trials is an ongoing challenge resulting from the continuous advancement in computing, electronic and basic scien-ce driving rapid evolution of MRI acquisition/analysis techniques. Some methods (e.g. functional MRI (fMRI), perfusion,tractography) are conceptually complex and when commercially available they require specialized knowledge for optimizeddata acquisition, analysis and/or interpretation. They also require complex data analysis software usually developed andlicensed in the research rather than clinical domain. In some patient groups the presence of MR conditional implants posesadditional MRI safety concerns. Furthermore, the clinical use of non commercial specialized software and MRI sequenceshas implications under the Medical Devices Directive. These issues pose technical and regulatory challenges that may lieoutside the professional scope of radiologists or neurosurgeons.Our Hospital embraced the challenge of translating advanced MRI methods in the clinical practice since 2002. Our Neu-roradiology department promotes strong collaborations between MRI clinical scientists (accredited healthcare physicists)and radiologists, two specialized groups forming a collaborative link with internationally recognized neuroscientists andneurosurgeons, a strategy proving highly successful. Effective management of quality control and patient safety are fun-damental to our approach.We will present results from: the optimization of sequence contrast and MRI safety for the implantation of deep brain sti-mulation (DBS) in Parkinson’s patients; novel fMRI studies in Parkinson’s patients with active DBS implants; the intra-ope-rative use of optic radiation tractography in medically refractory epilepsy patients undergoing temporal lobe resection; mu-scoskeletal imaging biomarker studies. A current focus is the introduction in clinical practice of perfusion techniques basedon arterial spin labeling to visualize perfusion territories.Our framework also promotes collaborations with pre-clinical researchers developing promising techniques (e.g CEST),and medical image computing specialists developing image manipulation and analysis software.

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STUDIO QUANTITATIVO IN AUTOMATICO DEL VOLUME DELL'AMIGDALA CON FREESURFER: CONFRONTO DIGRUPPO TRA DISLESSICI E CONTROLLI

M. Muti1, L. Busti1, A. Di Renzo1, P. Fattori3, D. Frondizi3, C. Piccolini3, M. Principi2

1U.O. Radioterapia Oncologica, A.O. S.Maria, Terni2U.O. Neuroradiologia, A.O. S.Maria, Terni3U.O. Neurofisiopatologia, A.O. S.Maria, Terni

Scopi: La letteratura evidenzia che la dislessia possa essere collegata a variazioni di volume e forma di alcune aree delsistema nervoso centrale, come ad esempio una riduzione del volume: della corteccia del lobo temporale sinistro, del loboanteriore destro del cervelletto, e una variazione di forma del corpo calloso. Il nostro lavoro è stato di verificare se esisteuna differenza di volume dell’amigdala tra un gruppo di dislessici e uno di controllo di pari età e sesso.Metodi: 17 dislessici (età_media±sd = (12.1±2.3) anni, range = 9-16 anni, 12 maschi e 5 femmine, dislessia valutata contest Sartori DDE-II previa valutazione cognitiva Q.I.>85 con scala di Wechsler WISC-III) e 11 controlli (età_media±sd= (11.8±1.7) anni, range = 9-15 anni, 5 maschi e 6 femmine) sono stati esaminati su tomografo da 3 Tesla (SiemensMagnetom Verio) tramite acquisizione di immagini RM isotropiche T1 dipendenti ad alta risoluzione e ad alto contrastotra grigia e bianca. Le immagini sono state successivamente elaborate con software FREESURFER (Martinos Center forBiomedical Imaging) che permette la segmentazione automatica delle strutture sottocorticali con valutazione finale del lorovolume. In fase di analisi statistica dei dati il volume dell’amigdala (Volume medio tra Dx e Sn) è stato valutato sia cometale che come rapporto con il volume intracranico da cui dipende linearmente.Risultati: Nel gruppo dei dislessici il volume medio dell’amigdala è rislutato pari a (1537±168) mm3 nel gruppo di controlloè risultato pari a (1693±192) mm3 la loro differenza è statisticamente significativa (p=0.04). Analogamente è risultatastatisticamente significativa la differenza del volume relativo dell’amigdala (mm3) rispetto al volume intracranico (cm3)tra dislessici (1.12±0.09) e controlli (1.20±0.07) (p=0.01). Non risulta statisticamente significativa la differenza tra volumeintracranico nei dislessici (1376±156) mm3 e controlli (1410±131) mm3 (p=0.54).Conclusioni: Nei Dislessici è stata evidenziata una riduzione del volume dell’amigdala che , nell’intervallo di età studiato, èrisultata pari a circa il 9%. Data la crescita del volume dell’amigdala con l’età è possibile esprimere tale riduzione di volumein termini di un ritardo dello sviluppo di 1.3 anni.

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Multi-parametric Magnetic Resonance study in ADHD patients

L. Biagi1, C. Pfanner1, A. Manfredi1, A. Tacchi1, S. Calderoni1, S. Millepiedi2, G. Masi1, M. Tosetti1

1IRCCS Fondazione Stella Maris, Pisa, Italy2Usl 11, Empoli, Firenze, Italy

Introduction.Several anatomical study by Magnetic Resonance Imaging have demonstrated the presence of volumetric alterations inchildren affected by Attention Deficit Hiperactivity Disorder (ADHD) [1,2]. Moreover, a partial dissociation of different frontalcircuits has been found by fMRI in ADHD subjects [3,4]. The aim of this work is to investigate no-invasively the cerebralstructure and metabolism of a group of ADHD children, by using MR multi-parametric techniques.Methods.Twenty-eight ADHD children/adolescents (age =7-17 years; mean±sd=12±3 years) participated at the study. At the timeof enrolment, none subject took any ADHD-specific pharmacological therapy. Clinical sample was compared to a con-trol group of 20 healthy subjects (mean±sd=11±3 years). MR exams were performed using a 1.5T GE human system(HDxt Signa, Healthcare GE, USA). The protocol lasted about thirty minutes and included both anatomical and metabo-lic series. In particular, beyond standard anatomical exam, we applied also 3D pCASL (post-labelling delay=1025 ms;FOV=240x240; spiral=512x8; slice thickness= 4mm, 3 NEX) for the measurement of cerebral perfusion and a 3D-high

resolution T1 weighted sequence (FSPGR, isotropic voxel=1mm3) for voxel-based morphometry (VBM).Results.VBM technique indicated an increase of the grey matter volume in ADHD subjects with respect to control subjects in theright superior frontal gyrus. Similarly, ADHD patients show an increase of white matter volume in the left superior frontalgyrus, in the cingulate gyrus and bilaterally in the inferior frontal gyrus. The comparison between the cerebral perfusionof the two groups shows a diffuse state of hypo-perfusion in the whole brain of ADHD no-treated patients. Increasing thestatistical threshold up to p<0.001, it is possible to highlight cerebral areas with major reduction of Cerebral Blood flow(CBF), such as the medial frontal gyrus, the middle temporal gyrus, the Cuneus bilaterally, as well the left inferior frontalgyrus and the right intraparietal cortex.References.[1] Cortese S. Eur J of Ped Neurology 2012; [2] Konrad K, Eickhoff SB. Human Brain Mapping 2010; [3] Roth RM SaykinAJ. Psychiatr Clin North Am 2004; [4] Sonuga Barke EJS, Castellanos FX. Neurosc and Biobeh Reviews 2007.

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ENTACAPONE REDUCES CORTICAL ACTIVATIONS IN PARKINSON'S DISEASE WITH WEARING-OFF: A FMRISTUDY

N. Tambasco1, S. Caproni1, M. Muti2, R. Tarducci4, P. Chiarini3, P. Nigro1, F. Ripandelli1, L. Parnetti1, P. Floridi3, A.

Rossi1, P. Calabresi1

1Clinica Neurologica, Azienda Ospedaliera-Università di Perugia2Servizio di Fisica Sanitaria, Azienda Ospedaliera di Terni3Servizio di Neuroradiologia, Azienda Ospedaliera di Perugia4Servizio di Fisica Sanitaria, Azienda Ospedaliera di Perugia5I.R.C.C.S. – Fondazione S.Lucia – Roma

Background and purpose: Wearing-off is one of the most frequent problems encountered by levodopa-treated patients.Entacapone, a peripheral inhibitor of catechol-O-methyltransferase (COMT), reduces this motor complication by prolongingthe effect of levodopa. We sought to understand the impact of COMT-inhibition on movement execution in PD patients withwearing-off by comparing functional magnetic resonance imaging (f-MRI) activation patterns prior to and during entacaponetreatment. Our hypothesis was to determine whether changes in cortical activation are associated to COMT-inhibitor treat-ment. Methods: Nine levodopa-treated non-demented PD patients with wearing-off were prospectively studied in two fMRIsession, prior to and during entacapone treatment. A group of control subjects were also studied for comparison. Results:The patients significant improved under COMT-inhibitor treatment based on home diaries. F-MRI results showed that atbaseline the patients presented a bilateral activation of the primary motor, controlateral premotor cortex and supplementarymotor area, as well as ipsilateral cerebellum. During treatment with entacapone, PD patients showed reductions in theactivations of these cortical areas and a decreased activation in the ipsilateral cerebellum. Conclusions: Our preliminaryfindings indicate that f-MRI is able to detect cortical activation changes during long-term modulation of dopaminergic treat-ment in PD patients with wearing-off, and thus, this technique could be further investigated in advanced PD patients.

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FUNCTIONAL CONNECTIVITY OF THE MOTOR CORTEX BY EEG-FMRI IN PARKINSON'S DISEASE

C. Testa1, G. Rizzo1, C. Tonon1, F. Pittau2, L. Ferri1, F. Bisquoli1, D.N. Manners1, S. Evangelisti1, L.L. Gramegna1, C.

Bianchini1, P. Cortelli1, P. Tinuper1, R. Lodi1

1Dip. Scienze Biomediche e Neuromotorie, Univ. Bologna2Service de Neurologie, Hôpitaux Univ Genève

Aim.We used EEG-fMRI to measure functional connectivity (FC) of brain motor network during resting state in patients withParkinson’s disease (PD) and to measure cortico-cortical synchronization between EEG channels, before and after L-dopatreatment.Methods.EEG-fMRI was acquired in 6 PD patients using a 1.5 T GE scanner equipped with an 8-channel head coil.Inclusion criteria were a diagnosis of PD “probable” and a therapy with only L-dopa. Exclusion criteria were moderate-severerest tremor, L-dopa-induced dyskinesia and evidence of gray or white matter abnormalities on conventional MRI. Patientswere examined in the early morning, before the intake of the first daily dose of L-dopa. They were tested by UPDRS. Afterthe EEG cap was placed on the patients, they were positioned in the scanner. Two runs of rest-BOLD acquisition wereacquired (each 6’45”, TR=3s, slice thickness 4 mm) in the “OFF” state. Patients exited the scanner and took L-dopa (100mg) and were repositioned in the scanner after the onset of the L-dopa effect. Two runs of rest-BOLD acquisition wereacquired in the “ON” state.FC inside the motor network was analyzed using a seed in the precentral gyrus (M1) and one in the Supplementary MotorArea (SMA). In both the “OFF” and “ON” conditions the statistics of the two runs were combined (singularly for each seed).Results and discussion.PD patients had a significantly increased FC during the “ON” state, in the sensorimotor and parietal dorsal attention network.This reflects how L-dopa improves motor performance by increasing the FC (Tessitore A et al 2012).Preliminary analyses of the EEG data were performed computing the coherence between channels C3-C4 (electrodes overM1). Cortico-cortical coherence was reduced after the onset of the L-dopa effect, suggesting a decrease in synchronization,paralleling the clinical improvement.Conclusion.The major fMRI finding in PD patients is an increase of FC of M1 and the posterior parietal lobe after L-dopa intake. Thismay be related to the effect of the L-dopa not only on motor performance but also on executive function.In future work (on a larger cohort) we will perform comparison of the EEG FC and the BOLD FC, and correlate fMRI andEEG findings with clinical variables.

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Simultaneous EEG/fMRI analysis in epilepsy: ICA and GLM approches.

L. Altabella1, M. Carnì2, C. Di Bonaventura3, J. Fattuch3, S. Casciato3, A.T. Giallonardo3, V. Nucciarelli3, C. Colonnese3, E.

Di Castro4, B. Maraviglia5

1Scuola di Specializzazione in Fisica Medica, Universita’ di Roma La Sapienza2Scuola di Dottorato in scienze morfofunzionali e biofisica Universita’ di Roma La Sapienza3Dip. di Neurologia e Psichiatria, Universita’ di Roma La Sapienza4UOC di Fisica Medica e Sanitari,, Policlinico Umberto I di Roma5Enrico Fermi Center, Dip. di Fisica, Universita’ di Roma La Sapienza

A simultaneous recording of electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) is a promi-sing tool in epilepsy [1] to detect regions of activation and deactivation in relation to interictal and ictal epileptic dischar-ge. The conventional analysis of EEG-fMRI data usually uses the general linear model (GLM) approach with regressorcreated by convolution of the EEG events with a standard hemodynamic response function (HRF). This approach hasmany limitations. Here we present a new approach to improve the epileptic events identification based on independentcomponent analysis (ICA) and EEG spectral analysis of simultaneous EEG/fMRI acquisitions on patients affected by ictalelectro-clinical activity. EEG recording was performed using a 32-channels MR-compatible device (Micromed, Italy). Twoseries of fMRI images (200 temporal dynamics) were acquired using a clinical 3T magnet (Siemens Verio). Seven epilepticsubjects were considered: partial seizure (n=4) and generalized (n=3) epilepsy. As regard data driven approach, spatialICA was performed with Group ICA Toolbox while model based was performed by GLM as implemented in SPM8. FMRIanalysis was carried out after image pre-processing, using a regressor obtained in the first case by convolving the spm-HRF with box-car function from EEG ictal events (identified by the neurophysiologist), and in the other by convolving thespm HRF with spectral profile of EEG data (processed with EEGLAB toolbox) and modelling the motion parameters asnuisance variables. The detected activation areas resulting from canonical analysis are in agreement with presumed elec-troclinical hypothesis. The same BOLD patterns of activation alone or activation-deactivation in response to synchronizedictal activity were found by ICA and conventional GLM analysis. However ICA and GLM-EEG spectrum analysis exhibitedan increased sensitivity for the detection of brain regions associated with epileptic events. Moreover, spectral EEG profilecan be a powerful and informative approach to reject ICA components more related to noise that to true activations. Thenovel method represents an improvements eliminating subjectivity in classification of the epileptic events.[1] Laufs, NeuroImage (2012), Aug 15;62(2):1056-67.

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MR ADVANCED STUDY IN NOCTURNAL FRONTAL LOBE EPILEPSY

C. Tonon1, L.L. Gramegna1, I. Naldi2, C. Testa2, D.N. Manners1, G. Rizzo1, L. Ferri2, F. Bisulli2, P. Tinuper2, R. Lodi1

1Functional MR, Policlinico S.Orsola-Malpighi, Dep. of Biomedical and Neuromotor Sciences, University of Bologna,Bologna, Italy2IRCCS Institute of Neurological Sciences of Bologna, Dep. of Biomedical and Neuromotor Sciences, University of Bologna,Bologna, Italy

ObjectiveNocturnal frontal lobe epilepsy (NFLE) includes paroxysmal episodes with polymorphic semeiology, and variable intensityand duration (Tinuper P. et al., 2011, 2010). The pathophysiology of the seizures in NFLE is not yet fully understood.Whereas some ictal features seem to be linked to fronto-mesial structures other manifestations, such as complex motorbehaviour are hard to confine to a specific cortical frontal area. Dystonic-dyskinetic elements suggest also a possibleinvolvement of subcortical structures like basal ganglia. Furthermore, NFLE seizures often seem to arise from sleep K-complex (or spindles), which originate in the thalamus.The aim of this study was to investigate the role of both cortical and subcortical metabolic and microstructural findings inthe physiopathology of NFLE.MethodsFrom July 2011 to June 2012, 20 patients (age: 36 ±10 years, 12 F) with clinical diagnosis of NFLE and 16 healthy controls(age: 32±7 years, 12 F) were evaluated with a standardized MRI protocol. The brain MR protocol (1.5 T GE) included: a) highresolution T1 and T2- weighted sequences for morphometric and voxel based morphometry (VBM) analyses, b) diffusiontensor imaging (DTI) for TBSS and tractografy analysis; c) single voxel proton MRS prescribed in the anterior cingulatedcortex and medial thalamus (TR=4000 ms, TE= 35 ms) (Lodi R. et al. 2009, Tonon C. et al. 2009). Group differenceswere calculated using the Student T-test. Correlations were performed between 1H-MRS and clinical parameters, usingthe Pearson test 1-tailed (statistical significance: p<0.05).ResultsThe mean disease duration was 23± 13 years, the mean age of patients at the onset of the disease was 11±7 years,the mean age at the diagnosis was 20±11 years. In the patients the cortical anterior cingulated [NAA+NAAG]/[Cr] ratiowas lower in comparison to healthy controls (p<0.01). No difference were found in the metabolites content of thalamuscompared to healthy controls. [NAA+NAAG]/[Cr] values were negatively correlated with clinical severity of NFLE (beta-0,473, p<0.05). VBM, TBSS and tractography analyses are under evaluation.ConclusionOur preliminary results show an involvement of the anterior cingulated cortex in the pathophysiology of NFLE. The role ofthe involvement of fronto-mesial structures will be elucidated integrating other advanced MR modalities results.

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Brain and body in pain: Magnetic Resonance applications in the investigation of neurophysiology of Pain

C. Cellini1

1Potsdam University . Dip. Sport- und Gesundheitswissenschaften

While clinical and experimental studies can show interactions between the intensity of pain sensation, pain unpleasantnessand emotions associated with reflection and behavior, brain imaging studies have unraveled pain transmitting structures.Via fMRI it has been found that the extent of medial prefrontal cortex (mPFC) deactivation correlated with the number ofyears of pain (Voss 2010). Grachev et al (via fMRI) found that the magnitude of the shift of the representation of the lowerback in the primary somatosensory cortex (S1) increases as the duration and intensity of pain increase (Grachev 2000).In a recent study, Wager et al. (Wager 2013) combined the use of functional magnetic resonance imaging (fMRI) withmachine learning, to develop a brain-based neurologic signature for experimental thermal pain. Reduced pain perceptionwhile being distracted from pain is an everyday example of how cognitive processes can interfere with pain perception.Using high-resolution functional magnetic resonance imaging of the human cervical spinal cord in combination with thermalpain stimulation and a well-established working memory task (Kirchner 1958) Sprenger et al. (Sprenger 2012) demonstratethat this phenomenon relies on an inhibition of incoming pain signals in the spinal cord. Neuronal responses to painfulstimulation in the dorsal horn of the corresponding spinal segment were significantly reduced under high working memoryload compared to low working memory load. In two functional magnetic resonance imaging (fMRI) experiments, (Wager2004) found that placebo analgesia was related to decreased brain activity in pain-sensitive brain regions and was asso-ciated with increased activity during anticipation of pain in the prefrontal cortex, providing evidence that placebos alterthe experience of pain. Another wide used technique to understand the brain structures is the voxel-based morphometry(VBM). This statistical has provided fairly compelling evidence of reduced gray matter in the DLPFC (Apkarian 2004; Sch-midt-Wilcke 2006), the right anterior thalamus, the brainstem, the somatosensory cortex and the posterior parietal cortex(Buckalew 2008) of people with Chronic pain. Apkarian et al. found that a combination of sensory and affective dimensionsof pain strongly predicted DLPFC gray matter changes. Schmidt-Wilcke et al. (Schmidt-Wilcke 2006) demonstrated strongcorrelations between the extent of density changes and pain intensity and unpleasantness.

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THE NEUROLOGICAL BASIS OF ATTACHMENT AND STRESS: A FUNCTIONAL MAGNETIC RESONANCE IMAGINGSTUDY

A. Agostini1, C. Testa1, F. Benuzzi2, D. Manners1, G. Rizzo1, E. Malucelli1, L. Gramegna1, C. Bianchini1, C. Tonon1, P.

Nichelli2, R. Lodi1

1Dip. Scienze Biomedice e NeuroMotorie, Università di Bologna2Dip. Scienze Biomediche, Metaboliche e Neuroscienze, Università di Modena e Reggio Emilia

Attachment is theorized as a biologically-based behavioral system developed during infancy and persisting throughout thelife span, to adapt the individual to meet the environmental demands. Attachment insecurity is believed to be associated withmaladaptive stress responses, thus representing a risk factor for the development of mental disorders. The neurobiologicalbasis of stress and attachment and their reciprocal interactions have yet to be completely elucidated. The aim of thisexplorative functional magnetic resonance imaging (fMRI) study was to investigate the influence of the insecure attachmentdimensions anxiety and avoidance on stress-evoked brain activity.Nineteen healthy volunteers underwent an fMRI scan while performing a stress-enhancing task. Participants filled out theattachment style questionnaire in order to assess the attachment dimensions anxiety over relationships and avoidance.The influence of attachment on the brain activity during stress was then assessed.Participants’ stress modulated blood oxygen level dependent (BOLD) signal changes were correlated to attachment anxietyin portions of the right medial frontal and parietal cortices encompassing the precuneus, precentral and postcentral gyrus,and posterior cingulate. No significant correlation was found between BOLD signal and attachment avoidance . The precu-neus and medial fronto-parietal cortex are involved in representation of the Self, memory of past experiences, and menta-lization: the preconditions for the functioning of the attachment system. As a result, our findings, linking attachment anxietyto brain activity in these neural structures, provide a suggestive frame of reference for the neural basis of attachment.This study corroborates the hypothesis of mutual interconnection between the neurocircuits of stress and attachment.Maladaptive stress response and attachment insecurity are recognized as interdependent risk factors for the developmentof psychopathologies. Enhanced knowledge of the neural correlates of attachment insecurity and stress may help to shedlight on the fundamental determinants for the development of psychological disorders.

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ANALISI RETROSPETTIVA DI 12 CASI DI LINFOMA CEREBRALE PRIMITIVO ESAMINATI CON RM MULTIMODALE

P. Chiarini1, M.G. Alagia1, A. Fiacca1, M.C. Gallina1, G. Guercini1, F. Leone1, R. Pantaleoni1, P. Floridi1

1S.C. di Neuroradiologia, Azienda Ospedaliero - Universitaria di Perugia

Il linfoma cerebrale primitivo (PCNSL) è un tumore la cui incidenza nei pazienti immunocompetenti è in continuo aumentonegli ultimi anni. Una diagnosi precoce all'imaging è cruciale in quanto il sospetto di linfoma condiziona fortemente lagestione del paziente, indirizzando gli accertamenti diagnostici verso la citologia liquorale o la biopsia cerebrale.Sebbene la neoplasia talvolta presenti aspetti caratteristici alla TC ed alla RM convenzionale, la diagnosi differenzialecon tumori frequenti come il glioblastoma multiforme (GBM) e le metastasi spesso non fornisce elementi di certezza. Neipazienti AIDS (in cui la malattia è in costante declino nell'ultimo decennio a seguito dell'introduzione della terapia HAART)la diagnosi differenziale si pone con la toxoplasmosi e la PML.La RM multimodale (RMM) è in grado di fornire importanti elementi differenziali; recenti dati preliminari sembrerebbero in-

dicare che la RMM può fornire inoltre alcuni elementi prognostici, consentendo di prevedere la risposta alla chemioterapia1.E' stata effettuata un'analisi retrospettiva di 12 casi di PCNSL esaminati con RM 1,5 e 3 T presso la struttura complessadi Neuroradiologia dell'Ospedale di Perugia. In particolare sono stati valutati i dati della diffusione (DWI), della perfusione(DSC) e della spettroscopia (1H-MRS) ed è stato verificato il grado di correlazione con la diagnosi istologica.I risultati preliminari hanno evidenziato valori di ADC e di rCBV significativamente più bassi rispetto ai GBM ed alle meta-stasi; si è rilevato inoltre un aspetto caratteristico della curva intensità-tempo. Un elemento distintivo di frequente riscontroalla 1H-MRS è stato quello di un elevato picco lipidico associato ad un alto rapporto Cho/Cr.Vengono discusse le implicazioni in termini di diagnosi differenziale e le possibili ricadute prognostiche e terapeutiche.1. F.E. Valles, C.L. Perez-Valles, S. Regalado, R.F. Barajas, J.L. Rubenstein, and S. Cha Combined Diffusion and PerfusionMR Imaging as Biomarkers of Prognosis in Immunocompetent Patients with Primary Central Nervous System Lymphoma.AJNR Am. J. Neuroradiol. 2013 34: 35-40

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FOLLOW-UP MR STUDY OF IDEBENONE THERAPY IN TEN PATIENTS CARRYING THE 3243 A>G TRNALEUMELAS MUTATION

C. Tonon1, C. La Morgia2, R. Liguori2, E. Malucelli1, M.L. Valentino2, G. Rizzo1, L. Iommarini2, R. Carroccia2, G.

Cantalupo2, M. Amadori2, M. Bellan2, R. Rinaldi3, P. Avoni2, A. Baruzzi2, V. Carelli2, R. Lodi1

1Functional MR Unit, Policlinico S.Orsola-Malpighi, Dep. of Biomedical and Neuromotor Sciences, University of Bologna,Bologna, Italy2IRCCS Institute of Neurological Sciences of Bologna, Dep. of Biomedical and Neuromotor Sciences, University of Bologna,Bologna, Italy3Unit of Neurology, Policlinico S. Orsola-Malpighi, Bologna, Italy

ObjectiveAnecdotal studies reported on idebenone therapy in patients with mitochondrial encephalomyopathy, lactic acidosis, andstroke-like episodes (MELAS).In the current study we assessed the efficacy of idebenone therapy in ten consecutively enrolled MELAS patients withvariable clinical phenotype by longitudinal clinical evaluation and quantitative measurements of bioenergetic markers inserum (lactic acid after standardized exercise), and in brain and skeletal muscle using magnetic resonance spectroscopy(MRS).MethodsWe studied longitudinally ten patients from four families, carrying different heteroplasmic loads of the 3243A>G/tRNALeumtDNA point mutation. Idebenone was given up to 675 mg/day and we assessed at two time points serum lactic acid afterexercise, brain proton (1H) and skeletal muscle phosphorus (31P) MRS, and clinical severity, as quantified by NewcastleMitochondrial disease adult scale.Brain single voxel 1H-MRS was performed using the point resolved spectroscopy (PRESS) sequence. In order to maximizethe detection of lactate (Kaufmann P. et al., 2004), a volume of interest (VOI) ranging from 4.8 to 14.2 cm3 was selected inthe lateral ventricles to include mostly the CSF (TE = 288, TR = 1500) (La Morgia C. et al., 2008; Grimaldi D.et al., 2010).31P-MRS investigations were performed as previously described (Lodi R. et al. 2004, 2011).ResultsOnly one patient had stroke-like episodes, whereas all others had variable degree of neuromuscular involvement, diabetes,deafness, gastrointestinal symptoms, nephropathy and cardiopathy.No significant changes in serum lactic acid, nor in brain lactate or muscle ATP synthesis evaluated in vivo were detectedafter therapy. Two patients died shortly after the follow-up evaluation. Some patients subjectively improved fatigability,cramps and gastrointestinal symptoms. Overall, the clinical assessment showed a progression of the disease in mostpatients. The current study, the largest so far, indicates that idebenone at this dosage did not significantly correct cerebraland muscle oxidative metabolism in MELAS patients.

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NEURORADIOLOGICAL AND NEUROMETABOLIC CHARACTERISATION OF CIPO PATIENTS

C. Tonon 1, L.L. Gramegna1, R. Rinaldi2, C. Testa1, D.N. Manners1, M. Amadori2, M.L. Valentino3, G. Cenacchi4, R.

Liguori3, L. Pironi5, V. Stanghellini6, V. Carelli3, R. De Giorgio6, R. Lodi1

1Functional MR Unit, Policlinico S.Orsola-Malpighi, Dep. of Biomedical and Neuromotor Sciences, University of Bologna,Bologna, Italy2Unit of Neurology, Policlinico S. Orsola-Malpighi, Bologna, Italy3IRCCS Institute of Neurological Sciences of Bologna, Dep. of Biomedical and Neuromotor Sciences, University of Bologna,Bologna, Italy4Dep. of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy5Center for Chronic Intestinal Failure, Policlinico S.Orsola-Malpighi, University of Bologna, Bologna, Italy6Department of Clinical Medicine and Digestive Diseases and Internal Medicine, Policlinico S. Orsola-Malpighi, Universityof Bologna, Bologna, Italy

ObjectiveThe main objective of this ongoing multidisciplinary study was to validate brain and skeletal muscle MR protocols in thediagnostic work-up of patients with chronic idiopathic intestinal pseudo-obstruction (CIPO). The specific objective was toidentify integrated patterns of changes suggestive for mitochondriopathies, using MR imaging (MRI) and spectroscopy(MRS.MethodsMR studies were performed in a 1.5 T GE whole-body scanner. The brain MR protocol included: a) high resolution T1-and T2- weighted sequences and b) diffusion tensor imaging (DTI), in order to detect signal intensity and volume changesof cortical and subcortical structures; c) brain proton MRS for the evaluation of ventricular lactate (La Morgia C. et al.,2008; Grimaldi D.et al., 2010).; and d) phosphorus MRS at rest and during an aerobic exercise to evaluate skeletal musclebioenergetics (Lodi R. et al. 2004, 2011).ResultsFrom 1 January 2008 to 1 July 2013 we evaluated with a standardized MRI protocol 40 patients with CIPO. In 6 patientsa severe leucoencephalopathy and an associated dysfunction of energetic metabolism were suggestive for mitochondrialneurogastrointestinal encephalomiopathy (MNGIE), as confirmed by the findings of mutations in the thymidine phospho-rylase gene. In other 3 patients with variable combination of clinical signs such as palpebral ptosis, ophthalmoparesis,hypoacusia or microsomia and brain and/or skeletal muscle bioenergetics defect, genetic analysis disclosed different pa-thogenic mtDNA mutation: 8344A>G (Myoclonic Epilepsy with Ragged Red Fibers, MERFF, n= 1), mutation in the mtDNApolymerase gamma (POLG) gene (n=1), and A1555A>G (n=1). In 16 patients with abnormal muscle and/or brain bioener-getics the mtDNA screening is still ongoing.Other brain MR features included metabolic encephalopathy (n=2); deposition of manganese in basal ganglia structureslikely secondary to long-term parenteral nutrition (n=8). One patient presented clinical and skeletal muscle MR alterationscompatible with myofibrillar myopathy, as confirmed by biopsy.ConclusionsOur preliminary results show a high prevalence of mitochondrial disorders in patients with CIPO and suggest that thescreening for mitochondrial defects should be included in the clinical work- up of these patients.

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DIFFUSION TENSOR STUDY OF BRAIN WHITE MATTER IN OPA1-DOMINANT OPTIC ATROPHY AND LEBER'SHEREDITARY OPTIC ATROPHY

D.N. Manners1, G. Rizzo1, C. La Morgia1, C. Tonon1, C. Testa1, P. Barboni3, E. Malucelli2, M.L. Valentino1, V. Carelli1, R.

Lodi1

1Dip Scienze Biomed. NeuroMotorie (DiBiNeM), Univ. Bologna, Bologna2Dip Farmacia Biotecnologia, Univ. Bologna, Bologna3Studio Oculistico d’Azeglio, Bologna

Objective: To study whole brain white matter of OPA1-dominant optic atrophy (OPA1-DOA) patients, compared with Leber'shereditary optic atrophy (LHON) patients and healthy controls, using diffusion tensor imaging, to detect subtle structuralalterations.Methods: 19 adult cases with OPA1-DOA, 17 with LHON and 19 healthy controls were studied. Imaging data were proces-sed to provide voxelwise estimates of tensor parameters, including mean diffusivity (MD) and fractional anisotropy (FA).Statistical analysis was focused on identifying areas of altered white matter compared with controls, and relate such alte-rations to clinical and genetic variables.Results: In LHON patients, half of the voxels with a significant diffusivity change were within the optic radiation and the otherhalf within other areas, the acoustic radiation being the most consistent. In OPA1-DOA patients the voxels were distributedthroughout the whole brain. Regression analyses revealed fewer changes in LHON patients taking idebenone. We alsofound a significant reduction in FA with age and higher MD in patients with a missense mutation in OPA1-DOA patients foralmost all regions; FA values directly correlated with average retinal nerve fiber layer thickness in several areas.Conclusions: LHON patients presented a preferential involvement of the optic radiation and of the acoustic radiation pos-sibly due to trans-synaptic degeneration, with a protective effect of idebenone therapy. OPA1-DOA patients presented awidespread involvement supporting the view of a multisystemic disorder (Yu-Wai-Man P et al, Brain 2010). The correlationbetween diffusivity abnormalities and the age of these patients also supports the hypothesis of a congenital and develop-mental disorder.

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MULTIPLANAR MORPHOMETRICS OF THE OPTIC CHIASM: FEASIBILITY OF A NOVEL MRI INDEX FORASSESSING WHITE MATTER ATROPHY IN MULTIPLE SCLEROSIS

F. Zaccagna1, T. Matys2, L. Wing2, N. Antoun2, T.F. Massoud3

1Department of Radiological, Oncological and Pathological Sciences - Sapienza University of Rome2Department of Radiology - University of Cambridge3Department of Radiology - Stanford University

Purpose: The ‘corpus callosum index’ was suggested as a marker for brain atrophy in multiple sclerosis (MS). However,this is limited by inter-subject variations in morphology, including sex differences and handedness. Therefore, we focusedon the optic chiasm (OC), a white matter (WM) structure related to the optic nerves (ONs), which are known to atrophy inMS, and readily accessible for measurement on routine brain MRI. We aimed to obtain detailed morphometrics in normaland MS patients. We then tested the hypothesis that smaller OCs are present in MS, aiding in eventual derivation of asimple and potentially clinically useful ‘optic chiasm index’ for evaluation of WM atrophy in MS patients.Materials & Methods: We retrospectively evaluated brain MRIs of 100 patients, 50 with unspecified MS histories, and 50with normal findings. An observer blinded to clinical data measured eight OC morphometrics on axial T2WIs: width, A/Pdiameter, diameters of each ON and optic tract (OT), and angles between individual ONs and OTs. The OC height wasmeasured on midsagittal T1WIs. We also measured the Evans’ index. For statistical comparison we used an unpairedsample t-test and the Mann–Whitney test for independent samples as appropriate (p-value <0.05).Results: Three patients were excluded owing to global atrophy. Mean age was 36.5yrs for the MS group and 46yrs forthe control group. Mean OC width, A/P diameter and height in patients with MS were, respectively, 11.6±0.9mm (CI 11.2–12.1), 2.73±0.55mm (CI 2.47–2.98) and 2.18±0.34mm (CI 2.03–2.3). In the normal group the values were 12.1±1.34mm(CI 11.5–12.6), 3.51±0.7mm (CI 3.19–3.83) and 2.3±0.27mm (CI 2.2–2.4). There was statistically significant differencebetween MS and normal patients for A/P diameter (p=0.000) and height (p=0.003), but not for width (p=0.237). The ONswere significantly smaller in MS (p=0.000), as were the OTs (p=0.004). Consequent to OC atrophy, the angle betweeneach ON was significantly wider (p=0.011) in MS, but not between each OT.Conclusion: The anterior visual pathway may offer a compelling model for evaluation of demyelinating disease elsewherein the CNS. The OC is significantly atrophic when examined in a mixed cohort of MS patients.Bibliography: Corpus callosum index and long-term disability in multiple sclerosis patients. Yaldizli O, Atefy R, Gass A,Sturm D, Glassl S, Tettenborn B, Putzki N. J Neurol. 2010 Aug;257(8):1256-64.