Does the default-mode functional connectivity of the brain correlate with working-memory performances?

The "default-mode" network is an ensemble of cortical regions that are typically deactivated during demanding cognitive tasks in functional magnetic resonance imaging (fMRI) studies. Using functional connectivity analysis, this network can be studied as a "stand-alone" brain system whose functional role is supposed to consist in the dynamic control of intrinsic processing activities like attention focusing and task-unrelated thought generation and suppression. Independent component analysis (ICA) is the method of choice for generating a statistical image of the "default-mode" network (DMN) using a task- and seed-independent distributed model of fMRI functional connectivity without prior specification of node region extent and timing of neural activation. We used a standard graded working-memory task (n-back) to induce fMRI changes in the default-mode regions and ICA to evaluate to DMN functional connectivity in nineteen healthy volunteers. Based on the known spatial variability of the ICA-DMN maps with the task difficulty levels, we hypothesized the ICA-DMN may also correlate with the subject performances. We confirmed that the relative extent of the anterior and posterior midline spots within the DMN were oppositely (resp. positively in the anterior and negatively in the posterior cingulate cortex) correlated with the level of task difficulty and found out that the spatial distribution of DMN also correlates with the individual task performances. We conclude that the working-memory function is related to a spatial re-configuration of the DMN functional connectivity, and that the relative involvement of the cingulate regions within the DMN might function as a novel predictor of the working-memory efficiency.

Phenylketonuria: white-matter changes assessed by 3.0-T magnetic resonance (MR) imaging, MR spectroscopy and MR diffusion.

PURPOSE: This study evaluated the sensitivity of a 3.0-Tesla (T) magnetic resonance imaging (MRI) in measuring cerebral phenylalanine using proton magnetic resonance spectroscopy and in assessing MR-documented white-matter changes by means of diffusion studies (diffusion-weighted imaging, apparent diffusion coefficient map; diffusion tensor imaging) in patients with phenylketonuria. MATERIALS AND METHODS: Thirty-two patients with the classical clinical and biochemical deficits of phenylketonuria underwent biochemical (blood phenylalanine), genotypic (phenylalanine hydroxylase gene) and radiological investigation by means of MRI, proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging with a 3.0-T scanner. RESULTS: Periventricular and subcortical white-matter changes were detected on all MR scans. In 29/32 patients, proton magnetic resonance spectroscopy easily documented abnormal signal elevation at 7.36 ppm, corresponding to phenylalanine, despite its low concentration. Phenylalanine signal amplitude relative to the creatine/phosphocreatine signal increased linearly with blood phenylalanine values (r 0.7067; p<0.001). Diffusion MRI demonstrated hyperintensity in the areas exhibiting MRI changes as well as decreased apparent diffusion coefficient values, but fractional anisotropy indices were normal. CONCLUSIONS: The high signal, together with better spectral, spatial, contrast and temporal resolution, makes the 3.0-T MR the most suitable technique in the study of the phenylketonuria. In particular, the multimodal approach with MRI, proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging can provide more information than previous studies performed with low-field systems.

Role of advanced MR imaging modalities in diagnosing cerebral gliomas.

The objective of this study was to evaluate the potential role of newly developed, advanced magnetic resonance (MR) imaging techniques (spectroscopy, diffusion and perfusion imaging) in diagnosing brain gliomas, with special reference to histological typing and grading, treatment planning and posttreatment follow-up. Conventional MR imaging enables the detection and localisation of neoplastic lesions, as well as providing, in typical cases, some indication about their nature. However, it has limited sensitivity and specificity in evaluating histological type and grade, delineating margins and differentiating oedema, tumour and treatment side-effects. These limitations can be overcome by supplementing the morphological data obtained with conventional MR imaging with the metabolic, structural and perfusional information provided by new MR techniques that are increasingly becoming an integral part of routine MR studies. Incorporation of such new MR techniques can lead to more comprehensive and precise diagnoses that can better assist surgeons in determining prognosis and planning treatment strategies. In addition, the recent development of new, more effective, treatments for cerebral glioma strongly relies on morphofunctional MR imaging with its ability to provide a biological interpretation of these characteristically heterogeneous tumours.

Role of perfusion-weighted imaging at 3 Tesla in the assessment of malignancy of cerebral gliomas.

PURPOSE: This study was performed to clarify the role of perfusion-weighted imaging (PWI) at 3 Tesla in the characterisation of haemodynamic heterogeneity within gliomas and surrounding tissues and in the differentiation of high-grade from low-grade gliomas. MATERIALS AND METHODS: We examined 36 patients with histologically verified gliomas (25 with high-grade and 11 with low-grade gliomas). PWI was performed by first-pass gadopentetate dimeglumine T2*-weighted echo-planar images, and cerebral blood volume (CBV) maps were computed with a nondiffusible tracer model. Relative CBV (rCBV) was calculated by dividing CBV in pathological areas by that in contralateral white matter. RESULTS: In high-grade gliomas, rCBV were markedly increased in mass [mean+/-standard deviation (SD), 4.3+/-1.2] and margins (4.0+/-1.1) and reduced in necrotic areas (0.3+/-0.3). Oedematous-appearing areas were divided in two groups according to signal intensity on T2-weighted images: tumour with lower (nearly isointense to grey matter) and oedema with higher (scarcely isointense to cerebrospinal fluid) signal intensity. Tumour showed significantly higher rCBV than did oedema (1.8+/-0.5 vs. 0.5+/-0.2; p<0.001) areas. In low-grade gliomas, mass (2.0+/-1.5) and margin (2.2+/-1.2) rCBV were significantly lower than in high-grade gliomas (p<0.001). CONCLUSIONS: Three-Tesla PWI helps to distinguish necrosis from tumour mass, infiltrating tumour from oedema and high-grade from low-grade gliomas. It enhances the magnetic resonance (MR) assessment of cerebral gliomas and provides useful information for planning surgical and radiation treatment.

3.0-T functional brain imaging: a 5-year experience.

The aim of this paper is to illustrate the technical, methodological and diagnostic features of functional imaging (comprising spectroscopy, diffusion, perfusion and cortical activation techniques) and its principal neuroradiological applications on the basis of the experience gained by the authors in the 5 years since the installation of a high-field magnetic resonance (MR) magnet. These MR techniques are particularly effective at 3.0 Tesla (T) owing to their high signal, resolution and sensitivity, reduced scanning times and overall improved diagnostic ability. In particular, the high-field strength enhances spectroscopic analysis due to a greater signal-to-noise ratio (SNR) and improved spectral, space and time resolution, resulting in the ability to obtain high-resolution spectroscopic studies not only of the more common metabolites, but also--and especially--of those which, due to their smaller concentrations, are difficult to detect using 1.5-T systems. All of these advantages can be obtained with reduced acquisition times. In diffusion studies, the high-field strength results in greater SNR, because 3.0-T magnets enable increased spatial resolution, which enhances accuracy. They also allow exploration in greater detail of more complex phenomena (such as diffusion tensor and tractography), which are not clearly depicted on 1.5-T systems. The most common perfusion study (with intravenous injection of a contrast agent) benefits from the greater SNR and higher magnetic susceptibility by achieving dramatically improved signal changes, and thus greater reliability, using smaller doses of contrast agent. Functional MR imaging (fMRI) is without doubt the modality in which high-field strength has had the greatest impact. Images acquired with the blood-oxygen-level-dependent (BOLD) technique benefit from the greater SNR afforded by 3.0-T magnets and from their stronger magnetic susceptibility effects, providing higher signal and spatial resolution. This enhances reliability of the localisation of brain functions, making it possible to map additional areas, even in the millimetre and submillimetre scale. The data presented and results obtained to date show that 3.0-T morphofunctional imaging can become the standard for high-resolution investigation of brain disease.

3.0-T morphological and angiographic brain imaging: a 5-years experience.

Ever since the introduction of magnetic resonance (MR), imaging with 1.5 Tesla (T) has been considered the gold standard for the study of all areas of the body. Until not long ago, higher-field MR equipment was exclusively employed for research, not for clinical use. More recently, the introduction of 3.0-T MR machines for new and more sophisticated clinical applications has resulted in important benefits, especially in neuroradiology. Indeed, their high gradient power and field intensity (3.0 T) allow adjunctive and more advanced diagnostic methodologies to be performed with excellent resolution in a fraction of the acquisition time required with earlier machines. The purpose of this paper is to illustrate the distinctive semeiological characteristics of 3.0-T morphological and angiographic brain imaging compared with lower-field systems and highlight the respective advantages and drawbacks based on the experience gained in the first 5 years from the installation of a 3.0-T magnet.

The pathogenesis of the white matter abnormalities in phenylketonuria. A multimodal 3.0 tesla MRI and magnetic resonance spectroscopy (1H MRS) study.

OBJECTIVE: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. METHODS: Thirty-two patients with phenylalanine hydroxylase deficiency (21 with early and 11 with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (1H MRS) investigation. RESULTS: All patients had white matter abnormalities on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1-weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues lambda(min), lambda(middle), lambda(max) obtained from DTI data, and the principal brain metabolites assessed by 1H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient's age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). CONCLUSIONS: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients.

Spectroscopic, diffusion and perfusion magnetic resonance imaging at 3.0 Tesla in the delineation of glioblastomas: preliminary results.

Recent advances in magnetic resonance imaging (MRI) have allowed the evaluation of metabolic, diffusion and hemodynamic features of malignant gliomas. The aim of this study was to evaluate whether such information provided useful, complementary information to conventional MRI for improving the evaluation of glioblastoma extent. Ten patients with glioblastoma multiforme underwent conventional MRI, proton MR spectroscopic imaging (1H-MRSI), perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI). Metabolite signals, including normalized choline, N-acetylaspartate, creatine and lactate/lipids, were obtained by 1H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI. In edematous-appearing areas, 3 multiparametric patterns were identified: infiltrating tumor, with abnormal metabolite ratios, lower ADC and higher rCBV; pure edema, with normal metabolite ratios, higher ADC and lower rCBV; and tumor-infiltrated edema, with abnormal metabolite ratios and intermediate ADC and rCBV. In normal-appearing areas, 2 multiparametric patterns were identified: tumor-infiltrated tissue, with abnormal metabolite ratios and higher rCBV; and normal tissue, with normal MR parameters. The combination of 1H-MRSI, DWI and PWI features contributed to delineation of glioblastomas, offering information not available with conventional MRI. This approach may enhance the assessment of brain gliomas, providing useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.

Supratentorial low-grade gliomas. Neuroradiology.

The radiologic modality that most likely provides the imaging information needed in a patient suspected of having a brain tumors is magnetic resonance imaging. A brain tumors can be reliably ruled out, if the standard magnetic resonance examination is performed properly and experts interpret the results as negative for tumor. In this paper we will illustrate morphological aspects of low-grade supratentorial neoplasms, including tumors of neuroepithelial tissue, such as low-grade diffuse fibrillary astrocytomas, and circumscribed astrocytic lesions (pilocytic astrocytoma, pleomorphic xantoastrocytoma and subependymal giant cell astrocytoma). Then the main practical applications of functional imaging in neurosurgery will be also debated.

Perfusion- and BOLD-based fMRI in the study of a human pathological model for task-related flow reductions.

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

High field functional MRI.

Functional magnetic resonance imaging (fMRI) has become the most widely used approach for studying brain functions in humans. The rapid and widespread diffusion of fMRI has been favoured by the properties this technique presents, and particularly by its sensitivity in analysing brain functional phenomena and by the lack of biological invasiveness, resulting in an unprecedented and unparalleled flexibility of use. These properties of fMRI brought the functional examination of the brain within the reach of the whole neuroscience community and have appreciably stimulated the research on the functional processes of the living brain. Among the main features of fMRI, its spatial and temporal resolution represents clear advantages compared with the other methods of functional neuroimaging. In fact, the high spatial resolution of fMRI permits to produce more precise and better localised information, and its temporal resolution provides the potential of a better understanding of neural dynamics at the level of single functional areas and of the neural constituents of functional patterns. A fundamental possibility of improving spatial and temporal resolution without excessively degrading signal-to-noise ratio consists in the use of high magnetic field intensity fMRI units. Besides, high field units make the use of more demanding fMRI paradigms, like single trial event related studies, much more compatible with the need of a solid statistical evaluation. This has notably promoted the diffusion of high field MRI units for human studies throughout the world, with very high field MRI units, up to 8 T, working in a few research centres, and a larger number of MRI units with field intensity ranging between 3 and 5 T.

High-field proton MRS of human brain.

Proton magnetic resonance spectroscopy (1H-MRS) of the brain reveals specific biochemical information about cerebral metabolites, which may support clinical diagnoses and enhance the understanding of neurological disorders. The advantages of performing 1H-MRS at higher field strengths include better signal to noise ratio (SNR) and increased spectral, spatial and temporal resolution, allowing the acquisition of high quality, easily quantifiable spectra in acceptable imaging times. In addition to improved measurement precision of N-acetylaspartate, choline, creatine and myo-inositol, high-field systems allow the high-resolution measurement of other metabolites, such as glutamate, glutamine, gamma-aminobutyric acid, scyllo-inositol, aspartate, taurine, N-acetylaspartylglutamate, glucose and branched amino acids, thus extending the range of metabolic information. However, these advantages may be hampered by intrinsic field-dependent technical difficulties, such as decreased T2 signal, chemical shift dispersion errors, J-modulation anomalies, increased magnetic susceptibility, eddy current artifacts, limitations in the design of homogeneous and sensitive radiofrequency (RF) coils, magnetic field instability and safety issues. Several studies demonstrated that these limitations could be overcome, suggesting that the appropriate optimization of high-field 1H-MRS would expand the application in the fields of clinical research and diagnostic routine.

MRI T-staging of laryngeal tumours: role of contrast medium.

Our aim was to evaluate the relative diagnostic accuracy of MRI without contrast medium and MRI before and after contrast medium in the assessment of T-staging of laryngeal tumours. We studied 25 men (mean age 51.8, range 41-61) with laryngeal squamous cell carcinomas, using Spin-echo (SE) T1-weighted and fast SE T2-weighted sequences. The T1-weighted sequences were then repeated after gadolinium-diethylene-triaminepenta-acetic acid (Gd DTPA) 0.1 ml/kg. All patients then underwent biopsy and surgery. Two radiologists independently assessed the anonymised images by filling-out two multiple-choice forms, one for each technique, at a 2 week interval. The forms included a judgement concerning tumour identification and infiltration of the anterior commissure, supraglottic region, arytenoid cartilage, Morgagni's ventricle, paraglottic space, thyroid and cricoid cartilages, thyro-hyo-epiglottic space, vocal cords, subglottic region, and epiglottis. Similar forms were filled out by the surgeon and the pathologist after surgery. The sensitivity, specificity and diagnostic accuracy of MRI were unaffected by the use of contrast medium. Since it did not provide additional staging information, its continued routine use in these cases is not justified.

Proton MR spectroscopy in connatal Pelizaeus-Merzbacher disease.

BACKGROUND: Pelizaeus-Merzbacher disease (PMD) is a rare dysmyelinating disorder characterised by early pendular nystagmus, often rotatory and muscular hypotonia with subsequent ataxia, spasticity and mental retardation. Various point mutations or duplications in the PLP gene on the X chromosome are responsible for PMD in the majority of patients. Autosomal recessive inheritance, particularly in the connatal form, cannot be excluded. Three different forms of the disease have been identified based on their onset, progression and severity of myelin pathology indicated by MRI features. Objective. To determine if MR spectroscopy is useful in the diagnosis of the connatal form of PMD. MATERIALS AND METHODS: Proton MR spectroscopy was performed on two children with connatal PMD. RESULTS: Our patients showed a markedly decreased peak of Cho. This alteration is well represented by quantitative analysis of the NAA-to-Cho ratio, which is the most important ratio affected. A significant decrease of the Cho-to-Cr ratio is also present. In the connatal form of PMD, global lack of myelination may be relevant, as demonstrated by a significant Cho peak reduction. CONCLUSIONS: Proton MR spectroscopy may be of diagnostic value in metabolic and destructive disorders of the brain. A greater number of patients with connatal PMD is needed in order to elucidate the significance of reduction of the Cho peak.

Osteochondroma of the L-5 vertebra: a rare cause of sciatic pain. Case report.

Solitary or multiple osteochondromas, which are benign bone tumors that usually occur in the long bones, are rarely found in the vertebral column. When present in the spine, however, they have a predilection for the cervical or upper thoracic regions. The authors present the case of a solitary osteochondroma arising from the left L-5 articular process that contributed to sciatica; complete cure was achieved following its removal. It is possible to speculate that the cartilage of secondary ossification centers can be the origin of aberrant islands of cartilaginous tissue that cause the osteochondroma to form. The more rapid the ossification process of these centers, the greater the probability that aberrant cartilage will form. Therefore, the fact that osteochondromas are more frequently located in the higher segments of the vertebral column could be explained by the different durations of the ossification processes in these centers, which increase gradually below the cervical segments.

Contrast-enhanced MR angiography (CE MRA) in the study of the carotid stenosis: comparison with digital subtraction angiography (DSA).

PURPOSE: To determine sensitivity, specificity and diagnostic accuracy of contrast-enhanced magnetic resonance angiography (CE MRA) compared to digital subtraction angiography (DSA) in the study of carotid stenosis. METHODS AND MATERIAL: We studied 23 patients with suspected cerebro-vascular insufficiency by carotid stenosis. Diagnostic examinations by means of CE MRA and DSA were carried out within 24 hours of each other. A 1.5 T superconductive magnet (Signa-General Electric) was used for CE MRA. This technique was performed using a fast spoiled gradient echo recalled (SPGR) sequence acquired in coronal plane 13 sec after injection of contrast medium. Imaging parameters were: TR/TE/FA 8 msec/1 msec/60 degrees, matrix 256 x 128, 1 excitation, FOV 18 x 13 cm, 28 slices per slab, slice thickness of 1 mm, acquisition time of 32 sec. The post-processing was performed using maximum intensity projection (MIP) and targeted MIP. For DSA examinations a Politron 1000 VR unit (Siemens) was used. RESULTS: In the identification and quantification of lesions, CE MRA showed values of 100%. In particular, in comparison to DSA, CE MRA was accurate in diagnosing all true negative and positive cases. The location of stenosis evaluated with CE MRA agreed in all cases with DSA. CONCLUSION: In our experience CE MRA proved to be a very valuable technique in diagnosing carotid stenosis, showing the same diagnostic accuracy as DSA. In this way CE MRA appears to be a substantial alternative technique to conventional MRA and other non-invasive diagnostic methods.

Proton magnetic resonance spectroscopy of the brain in pediatric patients.

H1-MRS is a non-invasive technique which provides different levels of information on brain tissue: the N-acetyl aspartate (NAA) is an indicator of neuronal development, the choline containing compound peak (Cho) provides information on myelination and on cell membrane turnover and gliosis, inositol (Ins) is considered a marker of neuronal degeneration. Lactate may be detected in presence of defective energy metabolism. In the perineonatal period, the brain is apt to be insulted by a variety of events including asphyxia, hypoxemia, hemorrhage, which may subsequently cause delay in development. It is clinically important to assess the degree of brain damage and to obtain the prognostic information in the neonatal and early infantile period. MRS has become available for clinical examinations of the brain during development and these techniques can be used to document improvement or the progression towards irreversible damage.

High-resolution magnetic resonance angiography of the internal carotid artery: 2D vs 3D TOF in stenotic disease.

The aim of this study was to compare high-resolution 2D TOF with high-resolution 3D TOF in the study of internal carotid artery disease. Sixty-four patients with clinical signs of cerebrovascular insufficiency were studied with a superconductive 1.5 T magnet using two techniques: 2D and 3D TOF. Digital subtraction angiography (DSA) was the gold standard. The 2D TOF technique was performed using the following parameters: TR/TE/FA/MA 49 ms/9 ms/60 degrees/512 x 256; the 3D TOF was performed with the following parameters: TR/TE/FA/MA 50 ms/8 ms/20 degrees/512 x 256. The 2D TOF agreed with DSA in 116 of 128 diagnostic judgments (90%) and overestimated seven times. The 3D TOF technique agreed with DSA in 125 of 128 diagnostic judgments (97%) with one overestimation and two underestimations. There was no statistically significant difference (P < 0.05) between the two different techniques. Our study confirms the high reliability of the methodology carried out with the high-resolution 2D and 3D technique.

MR angiography in carotid stenosis: a comparison of three techniques.

PURPOSE: To compare the accuracy of three different magnetic resonance angiography (MRA) techniques for studying steno-occlusive disease of carotid arteries. METHODS: 64 patients were evaluated with three MRA techniques- three-dimensional (3D) time-of-flight (TOF), two-dimensional (2D) TOF, and 3D Phase-Contrast (PC); the acquisition was in the axial plane, the volume included the carotid bifurcation. Digital subtraction angiography (DSA) was considered the 'gold standard'. The MRA images were reprojected with a maximum intensity pixel ray-tracing (MIP) algorithm. The three MRA techniques were blindly graded as normal, mildly stenotic (0-29%), moderately stenotic (30-49%), severely stenotic (70-99%), or occluded. RESULTS: DSA provided 128 diagnostic judgments: 92 were negatives and 36 positives. 2D TOF was in agreement with angiography in 116 of 128 cases (90%), but overestimated the results in seven cases and underestimated in five cases. 3D TOF agreed with angiography in 125 of 128 cases (97%), with one overestimation and two under estimations. 3D PC was concordant in 116 of 128 cases (90%), overestimating in six cases, underestimating in six cases. The sensitivity, specificity and diagnostic accuracy for 2D TOF was, respectively 84%, 94%, and 92%, while for 3D TOF was 94%, 100%, and 98%, and for 3D PC 86%, 98%, and 95%. The comparison of the three different MRA techniques provided no statistically significant difference (Friedman test P < 0.05). CONCLUSION: The high degree of diagnostic accuracy of MRA found in the study of the steno-occlusive disease of the carotid arteries confirms the high degree of reliability of this methodology carried out with the 3D TOF technique, compared to 2D TOF and 3D PC.