M De Luca

Advances in functional and structural MR image analysis and implementation as FSL.

The techniques available for the interrogation and analysis of neuroimaging data have a large influence in determining the flexibility, sensitivity, and scope of neuroimaging experiments. The development of such methodologies has allowed investigators to address scientific questions that could not previously be answered and, as such, has become an important research area in its own right. In this paper, we present a review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB). This research has focussed on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data. The majority of the research laid out in this paper has been implemented as freely available software tools within FMRIBs Software Library (FSL).

Evidence of early cortical atrophy in MS: relevance to white matter changes and disability.

Objective: To assess cortical gray matter (GM) changes in MS and establish their relevance to clinical disability and to inflammatory changes of white matter (WM) in patients with the relapsing–remitting (RR) and primary progressive (PP) forms of the disease. Methods: Conventional MRI examinations were obtained in patients with definite MS who had either the RR or the PP form of the disease. An automated analysis tool was used with conventional T1-weighted MR images to obtain total and cortical brain volumes normalized for head size. Total brain lesion load was estimated on conventional proton density and T2-weighted MR images. The relationship between volumetric MR measures and scores of clinical disability was assessed. Results: Normalized cortical volumes (NCV) were lower for both RR and PP MS patients than for normal control subjects (p < 0.001) but were similar between the two patient groups (p > 0.5). NCV decreases in both patients groups were detected even in those patients with short disease duration (<5 years; p < 0.001 in RR MS and p < 0.05 in PP MS) and minimal brain lesion volume (<5 mL; p < 0.0001 in RR MS and p < 0.005 in PP MS). Measures of NCV in individual patients were negatively correlated with T2-weighted lesion volume (r = −0.47, p < 0.001) and disease duration (r = −0.25, p < 0.05) only in the patients with RR MS. NCV correlated with Expanded Disability Status Scale scores across all of the patients, but the strength of the correlation was stronger (p < 0.05) for PP (r = −0.64, p < 0.0001) than for RR (r = −0.27, p = 0.04) MS patients. Conclusions: These data confirm substantial neocortical volume loss in MS patients and suggest that neocortical GM pathology may occur early in the course of the disease in both RR and PP MS patients and contribute significantly to neurologic impairment. Although a proportion of this neocortical pathology may be secondary to WM inflammation, the extent of the changes suggests that, especially in patients with PP MS, an independent neurodegenerative process also is active.

Blood oxygenation level dependent contrast resting state networks are relevant to functional activity in the neocortical sensorimotor system

The relevance of correlations between blood oxygenation level dependent (BOLD) signal changes across the brain acquired at rest (resting state networks, or RSN) to functional networks was tested using two quantitative criteria: (1) the localisation of major RSN correlation clusters and the task-related maxima defined in BOLD fMRI signal changes from the same subjects; and (2) the relative hemispheric lateralisation (LI) of BOLD fMRI signal changes in sensorimotor cortex. RSN were defined on the basis of signal changes correlated with that of a “seed” voxel in the primary sensorimotor cortex. We found a generally close spatial correspondence between clusters of correlated BOLD signal change in RSN and activation maxima associated with hand movement. Conventional BOLD fMRI during active hand movement showed the expected wide variation in relative hemispheric lateralisation of LI for sensorimotor cortex across the subjects. There was a good correlation between LIs for the active hand movement task and the RSN (r=0.74, p<0.001). The RSN thus define anatomically relevant regions of motor cortex and change with functionally relevant variations in hemispheric lateralisation of sensorimotor cortical interactions with hand movement.

Prominent brain axonal damage and functional reorganization in “pure” adrenomyeloneuropathy

Background: Cerebral involvement is usually absent in pure adrenomyeloneuropathy (AMN). Recently, nonconventional MR studies have reported brain abnormalities in patients with pure AMN, providing evidence that occult cerebral involvement may occur in this disease. It remains unclear, however, whether these brain abnormalities reflect centripetal extension of spinal cord long-tract axonopathy or can be the expression of a pathologic process largely involving the brain. Methods: Conventional MRI and proton MR spectroscopic imaging (1H-MRSI) data of four patients with pure AMN were compared to those of four men with spinal cord injury (SCI) and 10 age-matched healthy men (HM). Resonance intensity areas of N-acetylaspartate (NAA) and choline were calculated as ratios to creatine (Cr) in voxels located in white matter (WM) regions. Functional MRI (fMRI) data during simple motor task were obtained in a separate session in three patients with AMN and three age-matched HM. Results: Conventional MRI examinations were normal in all patients. On 1H-MRSI, NAA/Cr values were lower in all WM regions of patients with AMN than in those of patients with SCI (p < 0.05) and HM (p < 0.01). In contrast, patients with SCI showed NAA/Cr values lower than HM only in the periventricular WM (p = 0.04). At fMRI, patients with AMN showed a more pronounced activation than HM in all movement-associated cortical regions contralateral to the hand moved and an exclusive voxel activation of the primary motor, somatosensory, and posterior parietal cortices ipsilateral to the hand moved. Conclusions: CNS damage in pure adrenomyeloneuropathy is not confined exclusively to spinal cord and seems to primarily involve the brain. GLOSSARY: 1H-MRSI = proton MR spectroscopic imaging; AC = anterior commissure; AMN = adrenomyeloneuropathy; BOLD = blood oxygenation level dependent; BR = brisk reflexes; Cho/Cr = choline to creatine ratio; Cr = creatine; DTI = diffusion tensor imaging; EA = endocrine abnormalities; FLAIR = fluid-attenuated inversion recovery; fMRI = functional MRI; FMRIB = Functional Magnetic Resonance Imaging of the Brain; FILM = FMRIB’s improved linear model; Fr-WM = frontal WM; HM = healthy men; Lac = lactate; MD = motor deficits; NAA = N-acetylaspartate; Naa/Cr = N-acetylaspartate to creatine ratio; PC = posterior commissure; PD = proton density; Post-WM = deep posterior WM; Pv-WM = periventricular WM; SA = sensory abnormalities; SCI = spinal cord injury; SP = spastic paraparesis; Sph Dis = sphincteric disturbances; VLCFA = very-long-chain fatty acids; VOI = volume of interest; WM = white matter.

Direct intraarterial (ophthalmic artery) chemotherapy for advanced intraocular retinoblastoma: Five years experience

Purpose To report five years of conservative treatment for advanced retinoblastoma with the direct intra-arterial-ophthalmic artery infusion of Melphalan alone or Melphalan and Topotecan. Methods 75 children (82 eyes) with advanced retinoblastoma (Stage D-E/VA –VB) were entered in phase two of one center open study-approved protocol of ophthalmic artery infusion (Italian intra-arterial protocol, approved by the Ethic Commettee – University Hospital of Siena). Seven cases have been treated bilaterally. 40 eyes were first diagnosis (naive) and 42 were relapses following chemotherapy and focal therapy and/or radiotherapy. Results Cannulation of the ophthalmic artery was performed by a femoral artery approach using microcatheters (magic 1.5) while the children were under general anesthesia and anticoagulated. Chemotherapy (Melphalan alone or Melphalan and Topotecan) was infused into the artery over a 30-minute period (dose of 3-7 mg of Melphalan and 0.3-0.4 mg of Topotecan, according to the age and size of the globe). Local and systemic toxicity have been evaluated and documented. Conclusion 75 children (82 eyes) with advanced retinoblastoma were eligible for the intra-arterial Italian Protocol. The 65.8% of all treated eyes is in complete remission. Superselective chemotherapy delivered through the ophthalmic artery can avoid enucleation, primary radiation or abuse of systemic chemotherapy.

069 Bis Chimiothérapie directe intra-artérielle (artère ophtalmique) avec du malphalan dans le traiement conservateur du rétinoblastome intra-oculaire

Objective To avoid enucleation cannulating repeatedly the ophthalmic artery of young children with advanced retinoblastoma and giving melphalan that is tumoricidal for retinoblastoma when given intraarterially. Materials 8 children with advanced retinoblastoma (Reese-Ellsworth stage V) eyes who were indicated for enucleation were entered in phase two of one center open study-approved protocol of ophthalmic artery infusion of melphalan to avoid enucleation. Methods cannulation of the ophthalmic artery was performed by a femoral artery approach using microcatheters while the children were under anesthesia and anti-coagulated. Chemotherapy (melphalan) was infused into the artery over a 30-minute period. Main outcome measures: ophthalmic examinations, retinal photography, and electroretinograms were used to document local toxicity, whereas physical examinations and complete blood counts were used to measure systemic toxicity. Results the ophthalmic arteries were successfully cannulated in 6 cases (total, 11 times). Dramatic regression of relapses was obtained into 4 cases, and of vitreous and subretinal seeds was observed in two cases. No severe systemic side effects (sepsis, anemia, neutropenia, fever, or death) occurred. No transfusions were required (red cells or platelets). Three patients developed lid rush that resolved without treatment in two days. There was no toxicity to the cornea, anterior segment, pupil, or motility. Conclusions we are experimenting a technique of direct ophthalmic artery infusion of melphalan for children with retinoblastoma. The technique has minimal systemic side effects and local toxicity. Therapeutic results in these 6 cases treated with this technique are reported and discussed.

Modulation by midazolam of brain areas related to anxiety induced by pain stimulation: An fMRI Study.

Introduction The study of anxiety, caused by threats of pain, and of brain regions related to it, has a growing interest because it is thought to play a role in the development of chronic pain. A previous study from our group (Ploghaus et al., 1999) showed that it is possible to discriminate between brain responses associated with the anticipation of pain and those associated with the direct experience of pain. They used a paradigm where contrasting-coloured lights signalled the delivery of painful heat, nonpainful warmth, or no stimulation. In particular, anticipation of pain activated sites within the medial frontal lobe and insular cortex. These “anticipation” areas are thought to also contain an anxiolytic component of pain processing.