Effect of Age on High T1 Signal Intensity of the Dentate Nucleus and Globus Pallidus in a Large Population Exposed to Gadodiamide.

OBJECTIVE: The purpose of this study was to assess the effect of age and number of previous injections of gadodiamide on the signal intensity of unenhanced T1-weighted (T1w) images of the dentate nucleus and globus pallidus in a large population. MATERIALS AND METHODS: A large, single-center retrospective population survey was designed and received institutional review board approval. Between January 2014 and December 2014, T1w signal intensity ratios were obtained from a large population of 2500 consecutive enhanced brain magnetic resonance imaging (MRI) scans. Of these, 1906 MRI scans of patients not previously exposed to any gadolinium (Gd)-based contrast agent were used as control group and were compared with 892 MRI scans of patients with documented prior exposure to intravenous gadodiamide. A quantitative study was conducted to assess the T1w signal intensity of dentate nucleus-to-pons (Dn/Po) and globus pallidus-to-thalamus (Gp/Th) ratios. Multiple regression analysis was used to test the effect of age, time delay, and number of previous Gd-based contrast agent injections as predictor variables of T1w signal intensity ratios. RESULTS: In the Gd-exposed patients, multivariate regression analysis showed age (ß = -0.285; P < 0.0001) and the number of previous injections of gadodiamide (ß = 0.224; P < 0.0001) to be powerful predictors of Dn/Po ratio. Similarly, age (ß = 0.269; P < 0.0001) and the number of previous injections of gadodiamide (ß = 0.127; P < 0.0001) predicted Gp/Th ratio. CONCLUSIONS: In this study, we confirm that the number of previous gadodiamide injections is a powerful predictor of the signal intensity increase of the Dn/Po and Gp/Th ratios on unenhanced T1w images and demonstrate that aging influences the T1 signal intensity of DN and GP in Gd-naïve and in Gd-exposed subjects.

White Matter Microstructural Changes Following Quadrato Motor Training: A Longitudinal Study.

Diffusion tensor imaging (DTI) is an important way to characterize white matter (WM) microstructural changes. While several cross-sectional DTI studies investigated possible links between mindfulness practices and WM, only few longitudinal investigations focused on the effects of these practices on WM architecture, behavioral change, and the relationship between them. To this aim, in the current study, we chose to conduct an unbiased tract-based spatial statistics (TBSS) analysis (n = 35 healthy participants) to identify longitudinal changes in WM diffusion parameters following 6 and 12 weeks of daily Quadrato Motor Training (QMT), a whole-body mindful movement practice aimed at improving well-being by enhancing attention, coordination, and creativity. We also investigated the possible relationship between training-induced WM changes and concomitant changes in creativity, self-efficacy, and motivation. Our results indicate that following 6 weeks of daily QMT, there was a bilateral increase of fractional anisotropy (FA) in tracts related to sensorimotor and cognitive functions, including the corticospinal tracts, anterior thalamic radiations, and uncinate fasciculi, as well as in the left inferior fronto-occipital, superior and inferior longitudinal fasciculi. Interestingly, significant FA increments were still present after 12 weeks of QMT in most of the above WM tracts, but only in the left hemisphere. FA increase was accompanied by a significant decrease of radial diffusivity (RD), supporting the leading role of myelination processes in training-related FA changes. Finally, significant correlations were found between training-induced diffusion changes and increased self-efficacy as well as creativity. Together, these findings suggest that QMT can improve WM integrity and support the existence of possible relationships between training-related WM microstructural changes and behavioral change.

Increased Alpha Band Functional Connectivity Following the Quadrato Motor Training: A Longitudinal Study.

Quadrato Motor Training (QMT) is a new training paradigm, which was found to increase cognitive flexibility, creativity and spatial cognition. In addition, QMT was reported to enhance inter- and intra-hemispheric alpha coherence as well as Fractional Anisotropy (FA) in a number of white matter pathways including corpus callosum. Taken together, these results seem to suggest that electrophysiological and structural changes induced by QMT may be due to an enhanced interplay and communication of the different brain areas within and between the right and the left hemisphere. In order to test this hypothesis using the exact low-resolution brain electromagnetic tomography (eLORETA), we estimated the current neural density and lagged linear connectivity (LLC) of the alpha band in the resting state electroencephalography (rsEEG) recorded with open (OE) and closed eyes (CE) at three different time points, following 6 and 12 weeks of daily QMT. Significant changes were observed for the functional connectivity. In particular, we found that limbic and fronto-temporal alpha connectivity in the OE condition increased after 6 weeks, while it enhanced at the CE condition in occipital network following 12-weeks of daily training. These findings seem to show that the QMT may have dissociable long-term effects on the functional connectivity depending on the different ways of recording rsEEG. OE recording pointed out a faster onset of Linear Lag Connectivity modulations that tend to decay as quickly, while CE recording showed sensible effect only after the complete 3-months training.

Regional MRI Diffusion, White-Matter Hyperintensities, and Cognitive Function in Alzheimer's Disease and Vascular Dementia.

BACKGROUND AND PURPOSE: An increase in brain water diffusivity as measured using magnetic resonance imaging (MRI) has been recently reported in normal-appearing white matter (NAWM) in patients affected by cognitive impairment. However, it remains to be clarified if this reflects an overt neuronal tissue disruption that leads to degenerative or microvascular lesions. This question was addressed by comparing the regional MRI apparent diffusion coefficients (ADCs) of NAWM in patients affected by Alzheimer's disease (AD) or vascular dementia (VaD). The relationships of ADCs with the white-matter hyperintensity (WMH) burden, carotid atherosclerosis, and cognitive performance were also investigated. METHODS: Forty-nine AD and 31 VaD patients underwent brain MRI to assess the WMH volume and regional NAWM ADCs, neuropsychological evaluations, and carotid ultrasound to assess the plaque severity and intima-media thickness (IMT). RESULTS: Regional ADCs in NAWM did not differ between VaD and AD patients, while the WMH volume was greater in VaD than in AD patients. The ADC in the anterior corpus callosum was related to the WMH volume, while a greater carotid IMT was positively correlated with the temporal ADC and WMH volume. The memory performance was worse in patients with higher temporal ADCs. Constructional praxis scores were related to ADCs in the frontal, and occipital lobes, in the anterior and posterior corpus callosum as well as to the WMH volume. Abstract reasoning was related to frontal, parietal, and temporal ADCs. CONCLUSIONS: Our data show that higher regional ADCs in NAWM are associated with microcirculatory impairment, as depicted by the WMH volume. Moreover, regional ADCs in NAWM are differently associated with the neuropsychological performances in memory, constructional praxia, and abstract reasoning domains.

Magnetic resonance imaging differential diagnosis of brainstem lesions in children.

Differential diagnosis of brainstem lesions, either isolated or in association with cerebellar and supra-tentorial lesions, can be challenging. Knowledge of the structural organization is crucial for the differential diagnosis and establishment of prognosis of pathologies with involvement of the brainstem. Familiarity with the location of the lesions in the brainstem is essential, especially in the pediatric population. Magnetic resonance imaging (MRI) is the most sensitive and specific imaging technique for diagnosing disorders of the posterior fossa and, particularly, the brainstem. High magnetic static field MRI allows detailed visualization of the morphology, signal intensity and metabolic content of the brainstem nuclei, together with visualization of the normal development and myelination. In this pictorial essay we review the brainstem pathology in pediatric patients and consider the MR imaging patterns that may help the radiologist to differentiate among vascular, toxico-metabolic, infective-inflammatory, degenerative and neoplastic processes. Helpful MR tips can guide the differential diagnosis: These include the location and morphology of lesions, the brainstem vascularization territories, gray and white matter distribution and tissue selective vulnerability.

Gadolinium-based contrast agents: did we miss something in the last 25 years?

In the last 24 months, several clinical and experimental studies, suggested first and demonstrated later, a progressive concentration of Gadolinium in the brain of normal renal function patients, following repeated injections of some of the commercially approved Gadolinium-Based Contrast Agents. Although, till now, Gadolinium brain deposits have not been associated to any kind of neurological signs or symptoms, they oblige the radiology community to modify the actual approach in using Gadolinium contrast media in daily practice, to reduce unknown possible risks for patients.

Elevation of Plasma 2-Arachidonoylglycerol Levels in Alzheimer's Disease Patients as a Potential Protective Mechanism against Neurodegenerative Decline.

BACKGROUND: Growing evidence suggests that the endocannabinoid system is involved in the pathogenesis of Alzheimer's disease (AD) and atherosclerosis. OBJECTIVE: The purpose of this study was to investigate the activation of the endocannabinoid system in AD in vivo and the possible intermediate role of atherosclerosis. METHODS: We enrolled 41 patients with probable AD, and 30 age- and gender-matched controls. All subjects underwent: ultrasound examination of cerebral and neck vessels (including intima-media thickness and plaque stenosis evaluation); blood sampling to measure levels of endocannabinoid [anandamide (AEA), 2-arachidonoylglycerol (2-AG)] and endogenous AEA analogues [N-palmitoyl-ethanolamide (PEA); N-oleoyl-ethanolamide]; neuropsychological evaluation and brain MRI (atrophy, white matter hyperintensity volume). RESULTS: 2-AG levels were higher in AD patients compared to controls (Mann-Whitney test p = 0.021). In the AD group, 2-AG correlated to white matter hyperintensity volume (r = 0.415, p = 0.015) and was higher in patients with chronic heart ischemic disease (p = 0.023). In AD patients, 2-AG was also positively related to memory (r = 0.334, p = 0.05) and attention (r = 0.423, p = 0.018) performances. Constructional praxia test scores were lower in patients with higher levels of PEA (r =-0.389, p = 0.019). CONCLUSION: AD patients present high plasma 2-AG levels, also in relation to heart ischemic disease and cerebral leukoaraiosis. This may be a protective mechanism hindering neurodegeneration, but it may also play an ambivalent role on cerebrovascular circulation. The increase in 2-AG and PEA levels observed with ongoing pathological processes may differently modulate cognitive performances.

Gadodiamide and Dentate Nucleus T1 Hyperintensity in Patients With Meningioma Evaluated by Multiple Follow-Up Contrast-Enhanced Magnetic Resonance Examinations With No Systemic Interval Therapy.

The dentate nucleus of the cerebellum may appear as hyperintense on unenhanced T1 magnetic resonance images (MRIs) of the brain. Recently, T1 signal hyperintensity has received attention owing to data on the association of this finding with the history of multiple injections of gadolinium-based contrast agents, specifically gadodiamide, in patients with multiple sclerosis and brain metastases. We conducted a retrospective study on patients with a meningioma who had routinely undergone follow-up enhanced MRI scans with gadodiamide. Across a time interval of 18 months (from January 2013 to July 2014), we identified 102 consecutive patients eligible for this study. A significant increase in T1 hyperintensity of the dentate nuclei of the cerebellum on nonenhanced scans was observed between the first and the last MRI in the group of patients with a history of at least 6 enhanced MRI scans (P < 0.01), whereas no differences were observed in the group with 1 to 5 enhanced MRI scans (P = 0.74). Further research is necessary to shed light on the mechanism of the T1 hyperintensity as well as on the histological and microstructural appearance of the dentate nucleus after multiple intravenous injections of gadodiamide. The finding raises the question of substantial dechelation of this agent in patients with normal renal function.

Inverse spatial distribution of brain metastases and white matter hyperintensities in advanced lung and non-lung cancer patients.

The aim of this study was to test by means of a voxel-based approach the hypothesis that there is a different spatial distribution of brain metastases (BM) and white matter hyperintensities (WMH) and that the presence of WMH affects the location of BM in lung and non-lung cancer patients. Two-hundred consecutive cancer patients at first diagnosis of BM were included. Images were acquired using a 1.5 Tesla MRI system (Magnetom Avanto B13, Siemens, Erlangen, Germany). Axial FLAIR T2 weighted images and gadolinium-enhanced T1 weighted images were post-processed for segmentation, co-registration and analysis. Binary lesion masks were created for WMH and BM, using Volumes of Interest. Lesion probability maps were generated and the voxel-based lesion-symptom mapping approach was used to model each voxel and to calculate a non parametric statistics (Brunner-Munzel test) describing the differences between the groups. In the lung cancer group we found higher frequency of BM in WMH- than in WMH+ patients in the occipital lobe and the cerebellum. In contrast, BM were more frequent in the right frontal lobe in WMH+ than in WMH- patients. We suggest that there exists an inverse brain spatial distribution between WMH and BM. In lung cancer patients, the presence of WMH seems to shift the distribution of BM toward locations different than what it is expected based on primary tumor.

Progressive increase of T1 signal intensity of the dentate nucleus on unenhanced magnetic resonance images is associated with cumulative doses of intravenously administered gadodiamide in patients with normal renal function, suggesting dechelation.

OBJECTIVES: The purpose of this study was to assess the association between the serial number of gadolinium-enhanced magnetic resonance imaging (MRI) examinations and the signal hyperintensity of the dentate nucleus on unenhanced T1-weighted images in patients with multiple sclerosis (MS) and those with brain metastases (BMs). MATERIALS AND METHODS: A group of 38 patients with MS and 37 patients with BM who had undergone at least 2 consecutive enhanced MRI examinations in our institution were examined for this retrospective observational study. The average T1 signal intensity of the dentate nuclei and the pons was obtained, and the dentate nuclei-to-pons (DNP) signal intensity ratio was calculated. These values were compared between patients with less than 6 and 6 enhanced MRI scans or more (eMRI). Relative changes of the DNP were plotted against the number of enhanced MRI scans (eMRIn). RESULTS: A progressive increase in the T1 signal intensity of the DNP ratio was observed both in the MS group and in the BM group. The DNP ratios of the last eMRI scans in the subgroup of patients with 6 eMRI scans or more were significantly higher than those of the first eMRI scan in the MS group (P < 0.001) and in the BM group (P < 0.01). Relative changes of the DNP showed a positive correlation with the eMRIn with a Spearman ρ of 0.96 (P < 0.001) in the MS group and that of 0.88 (P < 0.001) in the BM group. Curve regression analyses of the relative change of DNP ratios showed linear models to best fit the data with r(2) of 0.89 in the MS group and r(2) of 0.74 in the BM group. CONCLUSIONS: Our study shows that the increase in the unenhanced T1 signal intensity has a linear relationship with the eMRIn in patients with MS and BM. Indeed, we estimated a linear regression model to fit the progressive increase in T1 signal intensity of the dentate nucleus after multiple enhanced MRI scans. This finding suggests substantial dechelation of gadodiamide in patients with normal renal function, raising further concerns regarding the stability of this agent. Further comparative studies with other gadolinium chelates, specifically both linear and macrocyclic, are strongly recommended.

Bilateral remote cerebellar haemorrhage after spinal surgery: a case study and review of the literature.

BACKGROUND: Remote cerebellar haemorrhage is a rare and unpredictable complication after intracranial and spinal surgery, although less frequently found in the latter. The physiopathology of this phenomenon has not been definitely explained. OBJECTIVES: To describe and discuss the potential implications and pathomechanism of a bilateral remote cerebellar haemorrhage case after spinal surgery and review the literature related to this rare phenomenon. CASE REPORT: A 75 year-old man developed bilateral remote cerebellar haemorrhage after a lumbar laminectomy. Brain CT and MRI examinations showed chronic bilateral remote cerebellar haemorrhage, right haemoventricle and bilateral supratentorial subarachnoid haemorrhage. Subsequently, the patient underwent rehabilitation therapy with improvement of symptoms. CONCLUSION: When large cerebrospinal fluid loss is observed during spinal surgery, brain imaging study should be carried out. The pathogenetic hypothesis of microcirculation vessels tearing, the role of previous spinal surgery and of cerebellar atrophy should be considered and validated with further investigation.

Brain metastatic volume and white matter lesions in advanced cancer patients.

Brain white matter T2 hyperintensities (WMH) are a frequent MRI finding in adults, both in asymptomatic and in cancer patients. The aim of our study is to determine the relationship between quantitative measures of the volume of WMH and the volume of brain metastatic lesions at the first MRI diagnosis of brain metastases in a population of advanced cancer patients. Brain MRI examinations of 162 consecutive patients were included and 984 brain metastases at first diagnosis were studied. Axial FLAIR images were used to visualize peri-lesional edema and to segment WMH; multiplanar contrast-enhanced T1-weighted TSE images were used to detect, count, segment and measure metastatic lesions. Segmentation of WMH on FLAIR images was performed after linear image registration to eliminate peri-lesional edema from the WMH masks. The distribution of the volumes of metastatic lesions was significantly different (ANOVA, p = 0.003) among all patients and among lung cancer patients (ANOVA, p = 0.003), with higher volumes of metastatic lesions in a higher proportion of patients when WMH were absent. There were no significant differences among groups at the 10 cc threshold of WMH. We found that volumes of brain metastases at the first MR diagnosis in a sample of advanced cancer patients and in the group of lung cancer patients were significantly lower if WMH were present; we suggest that WMH may represent a clinical MRI bio-marker of brain micro-environment resistance to the occurrence of brain metastases.

Diffusion-weighted lesions after carotid artery stenting are associated with cognitive impairment.

The effect of carotid artery stenting (CAS) on cognitive function is still debated. Cerebral microembolism, detectable by post-procedural diffusion-weighted imaging (DWI) lesions, has been suggested to predispose to cognitive decline. Our study aimed at evaluating the effect of CAS on cognitive profile focusing on the potential role of cerebral microembolic lesions, taking into consideration the impact of factors potentially influencing cognitive status (demographic features, vascular risk profile, neuropsychological evaluation at baseline and magnetic resonance (MR) markers of brain structural damage). Thirty-seven patients with severe carotid artery stenosis were enrolled. Neurological assessment, neuropsychological evaluation and brain MR were performed the day before CAS (E0). Brain MR with DWI was repeated the day after CAS (E1), while neuropsychological evaluation was done after a 14-month median period (E2). Volumes of both white matter hyperintensities and whole brain were estimated at E0 on axial MR FLAIR and T1w-SE sequences, respectively. Unadjusted ANOVA analysis showed a significant CAS*DWI interaction for MMSE (F=7.154(32), p=.012). After adjusting for factors potentially influencing cognitive status CAS*DWI interaction was confirmed for MMSE (F=7.092(13), p=.020). Patients with DWI lesions showed a mean E2-E0 MMSE reduction of -3.1, while group without DWI lesions showed a mean E2-E0 MMSE of +1.1. Our study showed that peri-procedural brain microembolic load impacts negatively on cognitive functions, independently from the influence of patients-related variables.

Extra-spinal incidental findings at lumbar spine MRI in the general population: a large cohort study.

OBJECTIVE: To determine the prevalence of clinically and non-clinically relevant extra-spinal incidental findings (IF) in patients undergoing magnetic resonance imaging (MRI) of the lumbar spine and to evaluate the rate of undetected findings in archived radiological reports. METHODS: A retrospective search of patients undergoing lumbar spine MRI from January 2006 to December 2010 was conducted. By means of randomisation, we retrospectively reviewed 3,000 lumbar spine MRI examinations. Extra-spinal abnormalities were classified according to a modified CT Colonography Reporting and Data System (C-RADS). We retrospectively compared our structured approach with the archived MRI reports as it regarded the detection of extra-spinal IF to estimate non-detection rates. RESULTS: By means of the structured approach used, extra-spinal findings were detected in 2,060 (68.6 %) of the 3,000 lumbar spine MRI examinations; 362 (17.6 %) patients had indeterminate or clinically important findings (E3 and E4) requiring clinical correlation or further evaluation. After review of the original archived radiological reports, potentially important C-RADS E3 and E4 extra-spinal IF were respectively reported in 47 of the 265 (17.7 %) and in 8 of 74 (10.8 %) patients. CONCLUSIONS: Our study shows that incidental extra-spinal findings at conventional lumbar spine MRI are common but underestimated in radiological reports.

MR differential diagnosis of acute deep grey matter pathology in paediatric patients.

A high metabolic demand, rich vascularization and high concentrations of ionic elements leading to the generation of oxygen free radicals, give to the deep grey matter (DGM) nuclei specific susceptibility to both acute and chronic insults, especially in paediatric patients. Reaching a diagnosis in the early stages of acute diseases in many patients is crucial for instigating prompt specific therapy leading to a favourable outcome. On the basis of a review of a 10-year in-house database and a review of the literature on CNS pathology involving the DGM nuclei in paediatric patients, we summarize the MR findings and clinical clues that may help the radiologist in the difficult differential diagnosis process. The terms "acute" and "chronic" refer to the clinical onset of the disease. MR imaging allows the detection of an injury, determination of its precise anatomical location and characterization of the signal changes. This, combined with a knowledge of specific MRI patterns, may be a roadmap to a definite diagnosis. Clinical history, physical and laboratory findings, timing of the MR examination and advanced MR imaging techniques (diffusion-weighted imaging and (1)H-MR spectroscopy), are crucial in some patients.

Spatial brain distribution of intra-axial metastatic lesions in breast and lung cancer patients.

The frequency of the diagnosis of brain metastases has increased in recent years, probably due to an increased diagnostic sensitivity. Site predilection of brain lesions in oncological patients at the time of onset, may suggest mechanisms of brain-specific vulnerability to metastasis. The aim of the study is to determine the spatial distribution of intra-axial brain metastases by using voxel-wise statistics in breast and lung cancer patients. For this retrospective cross-sectional study, clinical data and MR imaging of 864 metastases at first diagnosis in 114 consecutive advanced cancer patients from 2006 to 2011 were included. Axial post-gadolinium T1 weighted images were registered to a standard template. Binary lesion masks were created after segmentation of volumes of interest. The voxel-based lesion-symptom mapping approach was used to calculate a t statistic describing the differences between groups. It was found that the lesions were more likely to be located in the parieto-occipital lobes and cerebellum for the total cohort and for the non small cell lung cancer group, and in the cerebellum for the breast cancer group. The voxel-wise inter-group comparisons showed the largest significant clusters in the cerebellum for the breast cancer group (p < 0.0008) and in the occipital lobe (p = 0.02) and cerebellum (p = 0.02) for the non small cell lung cancer group. We conclude a non-uniform distribution of metastatic brain lesions in breast and lung cancer patients that suggest differential vulnerability to metastasis in the different regions of the brain.

Differential effect of zoledronic acid on normal trabecular and cortical bone density in oncologic patients with bone metastases.

PURPOSE: To evaluate bone density changes at the level of normal bone and bone metastases after zoledronic acid (ZA) treatment in oncologic patients. MATERIALS AND METHODS: We retrospectively evaluated 72 consecutive adult patients with histologically confirmed solid tumors with at least 1 newly diagnosed bone metastatic lesion. Bone metastases were diagnosed by bone scans and confirmed with computed tomography (CT). Patients received intravenous ZA, 4 mg, by 15-min infusion every 28 day through a peripheral or a central venous access and were monitored for at least 3 months and a maximum of 24 months. Bone density was determined at the level of bone metastases and at the level of normal trabecular and cortical bone using a ROI-based approach. RESULTS: A significant increase was demonstrated at the level of normal trabecular bone of the calvarium and the femoral neck. No significant increase of density was observed at the level of the normal cortical bone. Bone metastases showed a significant increase in CT density as compared to baseline up to 24 months after zoledronic acid. CONCLUSION: We have found that long term treatment with ZA increases trabecular bone density in oncologic patients whereas normal cortical bone changes are not detectable.