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Aging leads to gray and white matter decline but their causation remains unclear. We explored two classes of models of age and dementia risk related brain changes. The first class of models emphasises the importance of gray matter: age and risk-related processes cause neurodegeneration and this causes damage in associated white matter tracts. The second class of models reverses the direction of causation: aging and risk factors cause white matter damage and this leads to gray matter damage. We compared these models with linear mediation analysis and quantitative MRI indices (from diffusion, quantitative magnetization transfer and relaxometry imaging) of tissue properties in two limbic structures implicated in age-related memory decline: the hippocampus and the fornix in 166 asymptomatic individuals (aged 38–71 years). Aging was associated with apparent glia but not neurite density damage in the fornix and the hippocampus. Mediation analysis supported white matter damage causing gray matter decline; controlling for fornix glia damage, the correlations between age and hippocampal damage disappear, but not vice versa . Fornix and hippocampal differences were both associated with reductions in episodic memory performance. These results suggest that fornix white matter glia damage may cause hippocampal gray matter damage during age-dependent limbic decline.

We provide a rich multi-contrast microstructural MRI dataset acquired on an ultra-strong gradient 3T Connectom MRI scanner comprising 5 repeated sets of MRI microstructural contrasts in 6 healthy human participants. The availability of data sets that support comprehensive simultaneous assessment of test-retest reliability of multiple microstructural contrasts (i.e., those derived from advanced diffusion, multi-component relaxometry and quantitative magnetisation transfer MRI) in the same population is extremely limited. This unique dataset is offered to the imaging community as a test-bed resource for conducting specialised analyses that may assist and inform their current and future research. The Microstructural Image Compilation with Repeated Acquisitions (MICRA) dataset includes raw data and computed microstructure maps derived from multi-shell and multi-direction encoded diffusion, multi-component relaxometry and quantitative magnetisation transfer acquisition protocols. Our data demonstrate high reproducibility of several microstructural MRI measures across scan sessions as shown by intra-class correlation coefficients and coefficients of variation. To illustrate a potential use of the MICRA dataset, we computed sample sizes required to provide sufficient statistical power a priori across different white matter pathways and microstructure measures for different statistical comparisons. We also demonstrate whole brain white matter voxel-wise repeatability in several microstructural maps. The MICRA dataset will be of benefit to researchers wishing to conduct similar reliability tests, power estimations or to evaluate the robustness of their own analysis pipelines.

APOE -ε4 is a main genetic risk factor for developing late onset Alzheimer’s disease (LOAD) and is thought to interact adversely with other risk factors on the brain. However, evidence regarding the impact of APOE -ε4 on grey matter structure in asymptomatic individuals remains mixed. Much attention has been devoted to characterising APOE -ε4-related changes in the hippocampus, but LOAD pathology is known to spread through the whole of the Papez circuit including the limbic thalamus. Here, we tested the impact of APOE -ε4 and two other risk factors, a family history of dementia and obesity, on grey matter macro- and microstructure across the whole brain in 165 asymptomatic individuals (38–71 years). Microstructural properties of apparent neurite density and dispersion, free water, myelin and cell metabolism were assessed with Neurite Orientation Density and Dispersion (NODDI) and quantitative magnetization transfer (qMT) imaging. APOE -ε4 carriers relative to non-carriers had a lower macromolecular proton fraction (MPF) in the left thalamus. No risk effects were present for cortical thickness, subcortical volume, or NODDI indices. Reduced thalamic MPF may reflect inflammation-related tissue swelling and/or myelin loss in APOE -ε4. Future prospective studies should investigate the sensitivity and specificity of qMT-based MPF as a non-invasive biomarker for LOAD risk.

Globally, at the time of writing (20 March 2021), 121.759.109 confirmed COVID-19 cases have been reported to the WHO, including 2.690.731 deaths. Globally, on 18 March 2021, a total of 364.184.603 vaccine doses have been administered. In Italy, 3.306.711 confirmed COVID-19 cases with 103.855 deaths have been reported to WHO. In Italy, on 9 March 2021, a total of 6.634.450 vaccine doses have been administered. On 15 March 2021, Italian Medicines Agency (AIFA) decided to temporarily suspend the use of the AstraZeneca COVID-19 vaccine throughout the country as a precaution, pending the rulings of the European Medicines Agency (EMA). This decision was taken in line with similar measures adopted by other European countries due to the death of vaccinated people. On 18 March 2021, EMA’s safety committee concluded its preliminary review about thromboembolic events in people vaccinated with COVID-19 Vaccine AstraZeneca at its extraordinary meeting, confirming the benefits of the vaccine continue to outweigh the risk of side effects, however, the vaccine may be associated with very rare cases of blood clots associated with thrombocytopenia, i.e., low levels of blood platelets with or without bleeding, including rare cases of cerebral venous thrombosis (CVT). We report the case of a 54-year-old woman who developed disseminated intravascular coagulation (DIC) with multi-district thrombosis 12 days after the AstraZeneca COVID-19 vaccine administration. A brain computed tomography (CT) scan showed multiple subacute intra-axial hemorrhages in atypical locations, including the right frontal and the temporal lobes. A plain old balloon angioplasty (POBA) of the right coronary artery was performed, without stent implantation, with restoration of distal flow, but with persistence of extensive thrombosis of the vessel. A successive thorax angio-CT added the findings of multiple contrast filling defects with multi-vessel involvement: at the level of the left upper lobe segmental branches, of left interlobar artery, of the right middle lobe segmental branches and of the right interlobar artery. A brain magnetic resonance imaging (MRI) in the same day showed the presence of an acute basilar thrombosis associated with the superior sagittal sinus thrombosis. An abdomen angio-CT showed filling defects at the level of left portal branch and at the level of right suprahepatic vein. Bilaterally, it was adrenal hemorrhage and blood in the pelvis. An evaluation of coagulation factors did not show genetic alterations so as the nasopharyngeal swab ruled out a COVID-19 infection. The patient died after 5 days of hospitalization in intensive care.

Phase contrast MRI (pcMRI) has been used to investigate flow pulsatility in cerebral arteries, larger cerebral veins, and the cerebrospinal fluid (CSF). Such measurements of intracranial pulsatility and compliance are beginning to inform understanding of the pathophysiology of conditions including normal pressure hydrocephalus, multiple sclerosis, and dementias. We demonstrate the presence of flow pulsatility in small cerebral cortical veins, for the first time using pcMRI at 7 T, with the aim of improving our understanding of the hemodynamics of this little-studied vascular compartment. A method for establishing where venous flow is pulsatile is introduced, revealing significant pulsatility in 116 out of 146 veins, across eight healthy participants, assessed in parietal and frontal regions. Distributions of pulsatility index (PI) and pulse waveform delay were characterized, indicating a small, but statistically significant ( < 0.05), delay of 59 ± 41 ms in cortical veins with respect to the superior sagittal sinus, but no differences between veins draining different arterial supply territories. Measurements of pulsatility in smaller cortical veins, a hitherto unstudied compartment closer to the capillary bed, could lead to a better understanding of intracranial compliance and cerebrovascular (patho)physiology.

Background Following the publication of the Italian Guidelines for the control and prevention of legionellosis an environmental and clinical surveillance has been carried out in Southeastern Italy. The aim of the study is to identify the risk factors for the disease, so allowing better programming of the necessary prevention measures. Methods During the period January 2000 - December 2009 the environmental surveillance was carried out by water sampling of 129 health care facilities (73 public and 56 private hospitals) and 533 buildings within the community (63 private apartments, 305 hotels, 19 offices, 4 churches, 116 gyms, 3 swimming pools and 23 schools). Water sampling and microbiological analysis were carried out following the Italian Guidelines. From January 2005, all facilities were subject to risk analysis through the use of a standardized report; the results were classified as good (G), medium (M) and bad (B). As well, all the clinical surveillance forms for legionellosis, which must be compiled by physicians and sent to the Regional Centre for Epidemiology (OER), were analyzed. Results Legionella spp. was found in 102 (79.1%) health care facilities and in 238 (44.7%) community buildings. The percentages for the contamination levels < 1,000, 1,000-10,000, > 10,000 cfu/L were respectively 33.1%, 53.4% and 13.5% for samples from health care facilities and 33.5%, 43.3% and 23.2% for samples from the community. Both in hospital and community environments, Legionella pneumophila serogroup ( L. pn sg) 2-14 was the most frequently isolate (respectively 54.8% and 40.8% of positive samples), followed by L. pn sg 1 (respectively 31.3% and 33%). The study showed a significant association between M or B score at the risk analysis and Legionella spp. positive microbiological test results (p < 0.001). From clinical surveillance, during the period January 2001 - August 2009, 97 cases of legionellosis were reported to the OER: 88 of community origin and 9 nosocomial. The most frequent symptoms were: fever (93.8%), cough (70.1%), dyspnea (58.8%), shivering (56.7%). Radiological evidence of pneumonia was reported in 68%. The laboratory diagnostic methods used were: urinary antigen (54.3%), single antibody titer (19.8%), only seroconversion (11.1%), other diagnostic methods (14.8%). Conclusions Our experience suggests that risk analysis and environmental microbiological surveillance should be carried out more frequently to control the environmental spread of Legionella spp. Furthermore, the laboratory diagnosis of legionellosis cannot be excluded only on the basis of a single negative test: some patients were positive to only one of the diagnostic tests.

To compare technical success, clinical success, complications and radiation dose for percutaneous intradiscal ozone therapy in patients with lumbar disc herniation using fluoroscopic guidance versus conventional computed tomography (CT) guidance. Between March 2018and March 2021, 124consecutive percutaneous intradiscal ozone therapies wereperformedon111 patients with low back pain (LBP) and/or sciatic pain due to lumbar disc herniation, using fluoroscopic or conventional CT guidance, respectively in 53 and 58 herniated lumbar discs, with at least 1-month follow up. Dose area product (DAP) and dose length product (DLP) were recorded respectively for fluoroscopy and CT, and converted to effective dose (ED). Fluoroscopic and CT groups were similar in terms of patient age (p-value 0.39), patient weight (p-value 0.49) and pre-procedure Oswestry Disability Index (ODI, p-value 0.94). Technical success was achieved in all cases. Clinical success was obtained in 83.02% (44/53) patients in fluoroscopic group and 79.31% (46/58) in CT group. Mean DAP was 11.63Gy*cm2 (range 5.42-21.61). Mean DLP was 632.49mGy-cm (range 151.51-1699). ED was significantly lower in the fluoroscopic group compared toCT group (0.34 vs. 5.53mSv, p = 0.0119). No major complication was registered. Minor complications were observed in 4 cases (2 in fluoroscopic group; 2 in CT group). Compared to conventional CT guidance, fluoroscopic guidance for percutaneous intradiscal ozone therapy in patients with lumbar disc herniation shows similar technical and clinical success rates, with lower radiation dose. This technique helps sparing dose exposure to patients.

Midlife obesity is a risk factor of late onset Alzheimer's disease (LOAD) but why this is the case remains unknown. As systemic inflammation is involved in both conditions, obesity-related neuroinflammation may contribute to damage in limbic structures important in LOAD. Here, we investigated the hypothesis that systemic inflammation would mediate central obesity related effects on limbic tissue microstructure in 166 asymptomatic individuals (38–71 years old). We employed MRI indices sensitive to myelin and neuroinflammation [macromolecular proton fraction (MPF) and kf] from quantitative magnetization transfer (qMT) together with indices from neurite orientation dispersion and density imaging (NODDI) to investigate the effects of central adiposity on the fornix, parahippocampal cingulum, uncinate fasciculus (compared with whole brain white matter and corticospinal tract) and the hippocampus. Central obesity was assessed with the Waist Hip Ratio (WHR) and abdominal visceral and subcutaneous fat area fractions (VFF, SFF), and systemic inflammation with blood plasma concentrations of leptin, adiponectin, C-reactive protein and interleukin 8. Men were significantly more centrally obese and had higher VFF than women. Individual differences in WHR and in VFF were negatively correlated with differences in fornix MPF and kf, but not with any differences in neurite microstructure. In women, age mediated the effects of VFF on fornix MPF and kf, whilst in men differences in the leptin and adiponectin ratio fully mediated the effect of WHR on fornix MPF. These results suggest that visceral fat related systemic inflammation may damage myelin-related properties of the fornix, a key limbic structure known to be involved in LOAD. •Central adiposity is linked to apparent myelin/inflammatory damage in the fornix.•Central adiposity is not linked to differences in apparent neurite microstructure.•Men were more centrally obese and had higher visceral fat fractions than women.•In women, age mediated the correlation between visceral fat and fornix myelin.•In men, adipokines mediated the correlation between WHR and fornix myelin.

The pulsatility of blood flow through cerebral arteries is clinically important, as it is intrinsically associated with cerebrovascular health. In this study we outline a new MRI approach to measuring the real-time pulsatile flow in cerebral arteries, which is based on the inflow phenomenon associated with fast gradient-recalled-echo acquisitions. Unlike traditional phase-contrast techniques, this new method, which we dub Dynamic Inflow Magnitude Contrast (DIMAC), does not require velocity-encoding gradients as sensitivity to flow velocity is derived purely from the inflow effect. We achieved this using a highly accelerated single slice EPI acquisition with a very short TR (15 ms) and a 90º flip angle, thus maximizing inflow contrast. We simulate the spoiled GRE signal in the presence of large arteries and perform a sensitivity analysis to demonstrate that in the regime of high inflow contrast it shows much greater sensitivity to flow velocity over blood volume changes. We support this theoretical prediction with in-vivo data collected in two separate experiments designed to demonstrate the utility of the DIMAC signal contrast. We perform a hypercapnia challenge experiment in order to experimentally modulate arterial tone within subjects, and thus modulate the arterial pulsatile flow waveform. We also perform a thigh-cuff release challenge, designed to induce a transient drop in blood pressure, and demonstrate that the continuous DIMAC signal captures the complex transient change in the pulsatile and non-pulsatile components of flow. In summary, this study proposes a new role for a well-established source of MR image contrast and demonstrates its potential for measuring both steady-state and dynamic changes in arterial tone.

Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) offers improved cellular specificity to microstructure-compared to water-based methods alone-but spatial resolution and SNR is severely reduced and slow-diffusing metabolites necessitate higher -values to accurately characterize their diffusion properties. Ultra-strong gradients allow access to higher -values per-unit time, higher SNR for a given -value, and shorter diffusion times, but introduce additional challenges such as eddy-current artefacts, gradient non-uniformity, and mechanical vibrations. In this work, we present initial DW-MRS data acquired on a 3T Siemens Connectom scanner equipped with ultra-strong (300 mT/m) gradients. We explore the practical issues associated with this manner of acquisition, the steps that may be taken to mitigate their impact on the data, and the potential benefits of ultra-strong gradients for DW-MRS. An in-house DW-PRESS sequence and data processing pipeline were developed to mitigate the impact of these confounds. The interaction of TE, -value, and maximum gradient amplitude was investigated using simulations and pilot data, whereby maximum gradient amplitude was restricted. Furthermore, two DW-MRS voxels in grey and white matter were acquired using ultra-strong gradients and high -values. Simulations suggest T -based SNR gains that are experimentally confirmed. Ultra-strong gradient acquisitions exhibit similar artefact profiles to those of lower gradient amplitude, suggesting adequate performance of artefact mitigation strategies. Gradient field non-uniformity influenced ADC estimates by up to 4% when left uncorrected. ADC and Kurtosis estimates for tNAA, tCho, and tCr align with previously published literature. In conclusion, we successfully implemented acquisition and data processing strategies for ultra-strong gradient DW-MRS and results indicate that confounding effects of the strong gradient system can be ameliorated, while achieving shorter diffusion times and improved metabolite SNR.