Sirio Cocozza

In vivo dentate nucleus MRI relaxometry correlates with previous administration of Gadolinium-based contrast agents

AbstractObjectivesTo evaluate changes in T1 and T2* relaxometry of dentate nuclei (DN) with respect to the number of previous administrations of Gadolinium-based contrast agents (GBCA).MethodsIn 74 relapsing-remitting multiple sclerosis (RR-MS) patients with variable disease duration (9.8±6.8 years) and severity (Expanded Disability Status Scale scores:3.1±0.9), the DN R1 (1/T1) and R2* (1/T2*) relaxation rates were measured using two unenhanced 3D Dual-Echo spoiled Gradient-Echo sequences with different flip angles. Correlations of the number of previous GBCA administrations with DN R1 and R2* relaxation rates were tested, including gender and age effect, in a multivariate regression analysis.ResultsThe DN R1 (normalized by brainstem) significantly correlated with the number of GBCA administrations (p<0.001), maintaining the same significance even when including MS-related factors. Instead, the DN R2* values correlated only with age (p=0.003), and not with GBCA administrations (p=0.67). In a subgroup of 35 patients for whom the administered GBCA subtype was known, the effect of GBCA on DN R1 appeared mainly related to linear GBCA.ConclusionsIn RR-MS patients, the number of previous GBCA administrations correlates with R1 relaxation rates of DN, while R2* values remain unaffected, suggesting that T1-shortening in these patients is related to the amount of Gadolinium given.Key Points• In multiple sclerosis, previous Gadolinium administrations correlate with dentate nuclei T1 relaxometry. • Such correlation is linked to linear Gadolinium chelates and unrelated to disease duration or severity. • Dentate nuclei T2* relaxometry is age-related and independent of previous Gadolinium administrations. • Changes in dentate nuclei T1 relaxometry are not determined by iron accumulation. • MR relaxometry can quantitatively assess Gadolinium accumulation in dentate nuclei.

Default-mode network changes in Huntington's disease: an integrated MRI study of functional connectivity and morphometry.

Previous MRI studies of functional connectivity in pre-symptomatic mutation carriers of Huntington’s disease (HD) have shown dysfunction of the Default-Mode Network (DMN). No data however are currently available on the DMN alterations in the symptomatic stages of the disease, which are characterized by cortical atrophy involving several DMN nodes. We assessed DMN integrity and its possible correlations with motor and cognitive symptoms in 26 symptomatic HD patients as compared to 22 normal volunteers, by analyzing resting state functional MRI data, using the Precuneal Cortex/Posterior Cingulate Cortices (PC/PCC) as seed, controlling at voxel level for the effect of atrophy by co-varying for gray matter volume. Direct correlation with PC/PCC was decreased, without correlation with atrophy, in the ventral medial prefrontal cortex (including anterior cingulate and subgenual cortex), right dorso-medial prefrontal cortex, and in the right inferior parietal cortex (mainly involving the angular gyrus). Negative correlations with PC/PCC were decreased bilaterally in the inferior parietal cortices, while a cluster in the right middle occipital gyrus presented increased correlation with PC/PCC. DMN changes in the ventral medial prefrontal cortex significantly correlated with the performance at the Stroop test (p = .0002). Widespread DMN changes, not correlating with the atrophy of the involved nodes, are present in symptomatic HD patients, and correlate with cognitive disturbances.

Biparametric 3T Magentic Resonance Imaging for prostatic cancer detection in a biopsy-naïve patient population: a further improvement of PI-RADS v2?

OBJECTIVES To prospectively determine the diagnostic accuracy of a biparametric 3T magnetic resonance imaging protocol (BP-MRI) for prostatic cancer detection, compared to a multiparametric MRI protocol (MP-MRI), in a biopsy naïve patient population. METHODS Eighty-two untreated patients (mean age 65±7.6years) with clinical suspicion of prostate cancer and/or altered prostate-specific antigen (PSA) levels underwent a MP-MRI, including T2-weighted imaging, diffusion-weighted imaging (with the correspondent apparent diffusion coefficient maps) and dynamic contrast enhanced sequence, followed by prostate biopsy. Two radiologists reviewed both the BP-MRI and the MP-MRI protocols to establish a radiological diagnosis. Receiver operating characteristics curves were obtained to determine the diagnostic performance of the two protocols. RESULTS The mean PSA level was 8.8±8.1ng/ml. A total of 34 prostatic tumors were identified, with a Gleason score that ranged from 3+3 to 5+4. Of these 34 tumors, 29 were located within the peripheral zone and 5 in the transitional zone. BP-MRI and MP-MRI showed a similar performance in terms of overall diagnostic accuracy, with an area under the curve of 0.91 and 0.93, respectively (p=n.s.). CONCLUSIONS BP-MRI prostate protocol is feasible for prostatic cancer detection compared to a standard MP-MRI protocol, requiring a shorter acquisition and interpretation time, with comparable diagnostic accuracy to the conventional protocol, without the administration of gadolinium-based contrast agent.

Improving signal-to-noise ratio in susceptibility weighted imaging: A novel multicomponent non-local approach

In susceptibility-weighted imaging (SWI), the high resolution required to obtain a proper contrast generation leads to a reduced signal-to-noise ratio (SNR). The application of a denoising filter to produce images with higher SNR and still preserve small structures from excessive blurring is therefore extremely desirable. However, as the distributions of magnitude and phase noise may introduce biases during image restoration, the application of a denoising filter is non-trivial. Taking advantage of the potential multispectral nature of MR images, a multicomponent approach using a Non-Local Means (MNLM) denoising filter may perform better than a component-by-component image restoration method. Here we present a new MNLM-based method (Multicomponent-Imaginary-Real-SWI, hereafter MIR-SWI) to produce SWI images with high SNR and improved conspicuity. Both qualitative and quantitative comparisons of MIR-SWI with the original SWI scheme and previously proposed SWI restoring pipelines showed that MIR-SWI fared consistently better than the other approaches. Noise removal with MIR-SWI also provided improvement in contrast-to-noise ratio (CNR) and vessel conspicuity at higher factors of phase mask multiplications than the one suggested in the literature for SWI vessel imaging. We conclude that a proper handling of noise in the complex MR dataset may lead to improved image quality for SWI data.

Alterations of functional connectivity of the motor cortex in Fabry disease An RS-fMRI study

Objective: To evaluate the presence of functional connectivity (FC) alterations of the motor circuits in patients with Fabry disease (FD) and their possible correlation with clinical variables with a resting-state (RS) fMRI analysis. Methods: In our cross-sectional study, 32 patients with FD with genetically confirmed classic diagnosis of FD (12 men, mean age 43.3 ± 12.2 years) were enrolled along with 35 healthy controls (HCs) of comparable age and sex (14 men, mean age 42.1 ± 14.5 years). RS-fMRI data were analyzed with a seed-based approach, with 2 different seeds for right and left motor cortex. Patients with FD underwent a clinical examination for the assessment of different motor functions. Correlations with clinical variables were probed with the Spearman correlation coefficient. Results: A reduction of FC was found in patients with FD compared to HCs between both motor cortices and 2 clusters encompassing, for each side, the caudate and lenticular nucleus (p < 5 × 10−4 and p < 10−8 for right and left motor cortex, respectively) and between the left motor cortex and dentate nuclei (p = 0.01) and Crus 1 in the right cerebellar hemisphere (p = 0.001). No significant results emerged in tests for possible correlations of FC with clinical scores. Conclusions: An alteration of the corticostriatal pathway is present in FD, in line with the recently suggested subclinical involvement of motor circuits in this disease. These results shed new light on the pattern of cerebral involvement in FD.

A Novel Multiparametric Approach to 3D Quantitative MRI of the Brain.

Magnetic Resonance properties of tissues can be quantified in several respects: relaxation processes, density of imaged nuclei, magnetism of environmental molecules, etc. In this paper, we propose a new comprehensive approach to obtain 3D high resolution quantitative maps of arbitrary body districts, mainly focusing on the brain. The theory presented makes it possible to map longitudinal (R 1), pure transverse (R 2) and free induction decay (R2*) rates, along with proton density (PD) and magnetic susceptibility (χ), from a set of fast acquisition sequences in steady-state that are highly insensitive to flow phenomena. A novel denoising scheme is described and applied to the acquired datasets to enhance the signal to noise ratio of the derived maps and an information theory approach compensates for biases from radio frequency (RF) inhomogeneities, if no direct measure of the RF field is available. Finally, the results obtained on sample brain scans of healthy controls and multiple sclerosis patients are presented and discussed.

Modifications of Resting State Networks in Spinocerebellar Ataxia Type 2

We aimed to investigate the integrity of the Resting State Networks in spinocerebellar ataxia type 2 (SCA2) and the correlations between the modification of these networks and clinical variables.

The combined use of conventional MRI and MR spectroscopic imaging increases the diagnostic accuracy in amyotrophic lateral sclerosis

PURPOSE We aimed to assess, in amyotrophic lateral sclerosis (ALS), the diagnostic accuracy of the combined use of conventional MRI signal changes (namely, hypointensity of the precentral cortex and hyperintensity of the corticospinal tracts on T2-weighted images), and N-Acetyl-Aspartate (NAA) reduction in the motor cortex at Magnetic Resonance Spectroscopy (MRS), which are affected by limited diagnostic accuracy when used separately. METHODS T2-hypointensity and NAA/(Choline+Creatine) ratio of the precentral gyrus and T2-hyperintensity of the corticospinal tracts were measured in 84 ALS patients and 28 healthy controls, using a Region-of-Interest approach. Sensitivity and specificity values were calculated using Fisher stepwise discriminant analysis, and cross-validated using the leave-one-out method. RESULTS Precentral gyrus T2 signal intensity (p<10(-4)) and NAA peak (p<10(-6)) were significantly reduced in patients, and their values did not correlate significantly to each other both in patients and controls, while no significant differences were obtained in terms of T2-hyperintensity of the corticospinal tract. Sensitivity and specificity of the two discriminant variables, taken alone, were 71.4% and 75.0%, for NAA peak, and 63.1% and 71.4% for T2-hypointensity, respectively. When using these two variables in combination, a significant increase in sensitivity (78.6%) and specificity (82.1%) was achieved. CONCLUSIONS Precentral gyrus T2-hypointensity and NAA peak are not significantly correlated in ALS patients, suggesting that they reflect relatively independent phenomena. The combined use of these measures improves the diagnostic accuracy of MRI in ALS diagnosis.

Cerebellum and neurodegenerative diseases: Beyond conventional magnetic resonance imaging

The cerebellum plays a key role in movement control and in cognition and cerebellar involvement is described in several neurodegenerative diseases. While conventional magnetic resonance imaging (MRI) is widely used for brain and cerebellar morphologic evaluation, advanced MRI techniques allow the investigation of cerebellar microstructural and functional characteristics. Volumetry, voxel-based morphometry, diffusion MRI based fiber tractography, resting state and task related functional MRI, perfusion, and proton MR spectroscopy are among the most common techniques applied to the study of cerebellum. In the present review, after providing a brief description of each technique’s advantages and limitations, we focus on their application to the study of cerebellar injury in major neurodegenerative diseases, such as multiple sclerosis, Parkinson’s and Alzheimer’s disease and hereditary ataxia. A brief introduction to the pathological substrate of cerebellar involvement is provided for each disease, followed by the review of MRI studies exploring structural and functional cerebellar abnormalities and by a discussion of the clinical relevance of MRI measures of cerebellar damage in terms of both clinical status and cognitive performance.

Cerebellar lobule atrophy and disability in progressive MS

Objective To investigate global and lobular cerebellar volumetries in patients with progressive multiple sclerosis (MS), testing the contribution of cerebellar lobular atrophy to both motor and cognitive performances. Methods Eighty-two patients with progressive MS and 46 healthy controls (HC) were enrolled in this cross-sectional study. Clinical evaluation included motor and cognitive testing: Expanded Disability Status Scale, cerebellar Functional System score, Timed 25-Foot Walk Test, 9-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test–Revised (BVMT) and California Verbal Learning Test II (CVLT). Cerebellar volumes were automatically obtained using the Spatially Unbiased Infratentorial Toolbox. A hierarchical multiple linear regression analysis was performed to assess the relationship between MRI variables of supratentorial and cerebellar damage (grey matter fraction, T2 lesion volume, metrics of cerebellar atrophy and cerebellar lesion volume) and motor/cognitive scores. Results Patients with MS exhibited lower cerebellar volumes compared with HC. Regression analysis showed that cerebellar metrics accounted for extra variance in both motor and cognitive performances, with cerebellar lesion volume, cerebellar Lobules VI, Crus I and VIIIa atrophy being independent predictors of 9-HPT, SDMT, BVMT and CVLT performances. Conclusions Atrophy of specific cerebellar lobules explains different aspects of motor and cognitive disability in patients with progressive MS. Investigation of cerebellar involvement provides further insight into the pathophysiological basis of clinical disability in progressive MS.