Cinzia Gavazzi

A functional magnetic resonance imaging study of patients with secondary progressive multiple sclerosis.

Although several functional magnetic resonance imaging (fMRI) studies have shown adaptive cortical changes in patients with early multiple sclerosis (MS), the presence of brain plasticity and its role in limiting the functional consequences of brain tissue damage in patients with secondary progressive (SP) MS have not been fully investigated yet. In this study, we assessed the movement-associated brain pattern of cortical activations in patients with SPMS and investigated whether the extent of cortical brain activations is correlated with the extent of brain structural changes. From 13 right-handed SPMS patients and 15 sex- and age-matched healthy volunteers, we obtained: (a) brain dual-echo scans; (b) brain mean diffusivity and fractional anisotropy maps of the normal-appearing white (NAWM) and gray matter (NAGM); (c) fMRI during the performance of simple motor tasks [flexion-extension of the last four fingers of the right hand (task 1) and flexion-extension of the right foot (task 2)]. Compared to healthy volunteers, during task 1 performance, SPMS patients showed more significant activations of the ipsilateral inferior frontal gyrus, middle frontal gyrus, bilaterally, and contralateral intraparietal sulcus. During task 2 performance, SPMS patients had more significant activations of the contralateral primary sensorimotor cortex and thalamus and of the ipsilateral upper bank of sylvian fessure. For both tasks, strong correlations (r values ranging from -0.83 to 0.88) were found between relative activations of cortical areas of the motor network and the severity of structural changes of the NAWM and NAGM. This study demonstrates that cortical plasticity does occur in patients with SPMS and that it might have a role in limiting the clinical impact of MS-related damage. It also suggests that, in these patients, functional abilities are sustained by increased recruitment of highly specialized cortical areas.

Single-voxel long TE 1H-MR spectroscopy of the normal brainstem and cerebellum

To evaluate the feasibility of single voxel 1H‐MRS of the CNS structures contained in the posterior cranial fossa and to determine the distribution of the normal metabolite ratios, concentrations, and T2 relaxation times in the midbrain, pons, medulla, dentate nucleus and cerebellar vermis.

Persistent contrast enhancement by sterically stabilized paramagnetic liposomes in murine melanoma

In the present research, we investigated the use of paramagnetic liposomes as contrast agents (CAs) for the detection of solid tumors. The liposomes were sterically stabilized by a polyethylene glycol (PEG) coating, and their size was constrained to ∼100 nm. Dimyristoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐diethylene‐triaminepentaacetate (DMPE‐DTPA) was used as the gadolinium‐carrying fatty acid chain. The relaxation properties were characterized through nuclear magnetic relaxation dispersion (NMRD) measurements, and analyzed with the use of theories and computer programs that are adequate for slowly rotating systems. Their relaxivity at 1.5 T was found to be acceptable for in vivo use. We then tested the liposomes against B16‐F10 murine melanomas using standard T1‐weighted schemes at 1.5 T, and concentrations corresponding to 0.03 mmol/kg of gadolinium (i.e., three to six times lower than the concentration of the small gadolinium complexes in clinical use). The blood half‐life was found to be 120 ± 20 min. The experiments show a good contrast enhancement in the tumor (33% ± 22%) 2 hr after administration, a further increase (43 ± 27%) 20 hr after administration, and a decrease (25% ± 14%) 54 hr after administration. High persistence of the CA was also observed in the liver and intestine, as expected in a hepatobiliar excretion pathway. Magn Reson Med 52:669–672, 2004.

ADC mapping of neurodegeneration in the brainstem and cerebellum of patients with progressive ataxias.

Analysis of the apparent diffusion coefficient (ADC) maps derived from diffusion-weighted MR imaging is emerging as a reproducible, sensitive, and quantitative tool to evaluate brain damage in diseases of the white and gray matter. To explore the potentials of ADC maps analysis in degenerative ataxias, we examined 28 patients and 26 age-matched controls with T1, T2, and diffusion (b values 0-1000 along the three main body axes)-weighted MR images. Twenty-four patients had inherited genetically proven diseases including spinocerebellar ataxia type 1 (SCA1) (n = 9), spinocerebellar ataxia type 2 (SCA2) (n = 8), and Friedreichs ataxia (FA) (n = 7), whereas four patients had sporadic adult onset pure cerebellar ataxia (three idiopathic, one gluten intolerance). Area and linear measurements of the CNS structures contained in the posterior cranial fossa (PCF) preliminary enabled classification of the patients in the three morphological categories reflecting the gross pathology findings, namely olivopontocerebellar atrophy (OPCA) (n = 10: six SCA2 and four SCA1), spinal atrophy (SA) (n = 7: all FA), and cortical cerebellar atrophy (CCA) (n = 4: three idiopathic and one gluten intolerance). Seven patients with SCA1 (n = 5) or SCA2 (n = 2) had morphologic changes reminiscent of OPCA, but their values were still in the lower normal range and were classified as undefined. Mean diffusivity (D) maps of the entire brain were generated and D was measured with regions of interest (ROI) in the medulla, pons, middle cerebellar peduncles, and the peridentate white matter. Moreover, after exclusion of the skull with manual segmentation and of the CSF with application of a threshold value, histograms were obtained for D of the brainstem and cerebellum and for D of the cerebral hemispheres. As compared to controls, a (P < 0.001) increase of D was observed in the medulla, middle cerebellar peduncles, and peridentate white matter in OPCA and undefined patients groups who had also significantly increased values of the 25th and 50th percentiles in the brainstem and cerebellum D histogram. In CCA (P = 0.01), an increase of the 25th and 50th percentile of the D value was observed in the brainstem and cerebellum histograms. The SA group showed (P < 0.001) an increased D in the medulla only. A correlation between clinical severity as assessed with the Inherited Ataxias Clinical Rating Scale (IACRS) and the 50th percentile of the D value in the brainstem and cerebellum histogram (r = 0.69) was observed in patients with SCA1 or SCA2. Diffusion MR imaging reveals variable patterns of increase of D in the brainstem, cerebellum, and cerebral hemispheres in degenerative ataxias that match the known distribution of the neuropathological changes.

Combining functional and structural brain magnetic resonance imaging in Huntington disease.

Objective: To concurrently investigate with magnetic resonance (MR) the brain activation and regional brain atrophy in patients with Huntington disease (HD). Methods: Nine symptomatic HD patients and 11 healthy subjects underwent an MR study including functional MR acquisition during finger tapping of the right hand and high-resolution T1-weighted images. Functional and structural data were analyzed using Statistical Parametric Mapping 2 software. Results: As compared with control subjects, HD patients showed decreased activation in the left caudate nucleus and medial frontal and anterior cingulate gyri and increased activation in the right supplementary motor area and supramarginal gyrus and left intraparietal sulcus. The pattern of atrophy included thinning of the gray matter (GM) in the insula, inferior frontal gyrus, caudate, lentiform nucleus, and thalamus, bilaterally, in the left middle frontal, middle occipital, and middle temporal gyri, and of periventricular, subinsular, right temporal lobe, and left internal capsule white matter. Only the decreased activation in the caudate nucleus correlated topographically with the caudate GM loss. Conclusion: The cortical areas of functional changes do not correspond to those of GM atrophy in patients with HD and are likely to reflect decreased output of the motor basal ganglia-thalamo-cortical circuit and compensatory recruitment of accessory motor pathways.

Self-paced frequency of a simple motor task and brain activation. An fMRI study in healthy subjects using an on-line monitor device.

Application of fMRI to clinical neurology implies the selection of a simple task and control of the task performance. The capability to objectively monitor variables related to task execution is, therefore, important and could improve accuracy of clinical fMRI studies. We assessed the influence of different self-paced frequencies of a simple motor task on brain activation in healthy subjects. A device was developed to measure the force exerted by a subject in pressing an air-filled rubber bulb with the last four fingers of the dominant hand. The task frequency was determined by analysis of the force signal. Nine healthy subjects performed twice the task with self-paced slow (0.35+/-0.09 Hz), intermediate (0.58+/-0.21 Hz) or fast (0.98+/-0.32 Hz) frequency. The device revealed impaired task execution in 1 subject. The coefficient of variation of frequency was 8.7% for slow, 12.2% for intermediate and 15.8% for fast paced task. No significant differences were found comparing the activation maps obtained at slow, intermediate and fast frequencies in the contralateral sensorimotor cortex and ipsilateral cerebellum. Cluster reproducibility was good for location (standard deviation<or=7.3 mm), but poor for signal intensity (coefficient of variation 0-176.8%) and extent (coefficient of variation 1.9-140.6%). In conclusion, self-paced frequency variations of a simple motor task in the 0.2-2 Hz range are not a relevant source of the variability of the fMRI results in healthy subjects. Use of the device for evaluation of the neurologically impaired patients might broaden the clinical applications of fMRI.

An fMRI study of the role of noise in image processing by the human perceptive system

Two psychophysics experiments are described, pointing out the significant role played by stochastic resonance in recognition of capital stylized noisy letters by the human perceptive apparatus. The first experiment shows that an optimal noise level exists at which the letter is recognized for a minimum threshold contrast. A simple two-parameter model that best fits the experimental data is also discussed. In the second experiment we show that a dramatically increased ability of the visual system in letter recognition occurs in an extremely narrow range of increasing noise. Possible interesting future investigations suggested by these experimental results and based on functional imaging techniques are discussed.