Gradient-echo MRI Research Articles

Selective brain entry of lipid nanoparticles in haemorrhagic stroke is linked to biphasic blood-brain barrier disruption.

Haemorrhagic stroke represents a significant public health burden, yet our knowledge and ability to treat this type of stroke are lacking. Previously we showed that we can target ischaemic-stroke lesions by selective translocation of lipid nanoparticles through the site of blood-brain barrier (BBB) disruption. The data we presented in this study provide compelling evidence that haemorrhagic stroke in mice induces BBB injury that mimics key features of the human pathology and, more importantly, provides a gate for entry of lipid nanoparticles-based therapeutics selectively to the bleeding site.Methods: Haemorrhagic stroke was induced in mice by intra-striatal collagenase injection. lipid nanoparticles were injected intravenously at 3 h, 24 h & 48 h post-haemorrhagic stroke and accumulation in the brain studied using in-vivo optical imaging and histology. BBB integrity, brain water content and iron accumulation were characterised using dynamic contrast-enhanced MRI, quantitative T1 mapping, and gradient echo MRI.Results: Using in-vivo SPECT/CT imaging and optical imaging revealed biphasic lipid nanoparticles entry into the bleeding site, with an early phase of increased uptake at 3-24 h post-haemorrhagic stroke, followed by a second phase at 48-72 h. Lipid nanoparticles entry into the brain post-haemorrhage showed an identical entry pattern to the trans-BBB leakage rate (Ktrans [min-1]) of Gd-DOTA, a biomarker for BBB disruption, measured using dynamic contrast-enhanced MRI.Discussion: Our findings suggest that selective accumulation of liposomes into the lesion site is linked to a biphasic pattern of BBB hyper-permeability. This approach provides a unique opportunity to selectively and efficiently deliver therapeutic molecules across the BBB, an approach that has not been utilised for haemorrhagic stroke therapy and is not achievable using free small drug molecules.

Altered Resting-State Intranetwork and Internetwork Functional Connectivity in Patients With Chronic Unilateral Vestibulopathy.

BackgroundChronic unilateral vestibulopathy (CUVP) is often accompanied by dizziness and postural instability, which restrict patients' daily activities. It is important to understand central compensation mechanisms underlying these symptoms in patients with CUVP by evaluating their brain functional status.PurposeTo analyze the changes in resting‐state intranetwork and internetwork functional connectivity (FC) and explore the state of central vestibular compensation in patients with CUVP.Study typeRetrospective.Population Eighteen patients with right‐sided CUVP and 18 age‐ and sex‐matched healthy controls.Field strength/sequenceA 3.0 T, three‐dimensional magnetization‐prepared rapid gradient‐echo (MP‐RAGE) and resting‐state echo‐planar imaging (EPI) functional MRI sequences.AssessmentFC alterations were explored using independent component analysis (ICA). Twelve independent components were identified via ICA. Dizziness Handicap Inventory (DHI) score for all patients was determined.Statistical testsTwo‐sample t test, family‐wise error (FWE) correction, Pearson correlation coefficient (r). A P value <0.05 was considered statistically significant.ResultsCompared with healthy controls, patients with CUVP showed significantly decreased FC in the right middle occipital gyrus within the lateral visual network, and significantly increased FC in the right supplementary motor area within the sensorimotor network. The FC was decreased between the medial visual and auditory networks, the right frontoparietal and posterior default networks, as well as the sensorimotor and auditory networks. There was a significant negative correlation between the FC changes in the visual, auditory networks and the DHI score in patients with CUVP (r = −0.583).Data conclusionCompared to healthy controls, the FC was significantly decreased in the right visual cortex and significantly enhanced in the right sensorimotor network in patients with CUVP. Patients with CUVP showed decreased FC between multiple whole‐brain networks, suggesting that abnormal integration of multisensory information may be involved in the occurrence of chronic dizziness and instability in patients with CUVP.Level of evidence4Technical EfficacyStage 2.

MRI longitudinal and cross‐sectional monitoring of amyloid pathology in non‐human primates

AbstractBackgroundThe potential for using MRI technologies to visualize amyloid deposits has been increasingly recognized. The present study utilized a New World non‐human primate (NHP) model of amyloid pathology, squirrel monkey (SQM), which unlike other NHPs, develops age‐dependent abundant cerebral amyloid angiopathy (CAA). The transverse relaxation rate (R2*) has a linear correlation with iron content, a component of amyloid deposits and microhemorrhages. Here we assessed whether the region of interest (ROI)‐based quantitative R2* assessment is able to detect differences in SQM neuropathology between varying age cohorts as well as longitudinally. An additional focus was to examine the presence of naturally occurring ARIA‐E like pathologies in geriatric SQMs.MethodMulti‐gradient echo (MGE) MRI datasets were acquired in three different SQM age cohorts at various stages of Aβ pathology development. The R2* maps were generated (Firevoxel parametric map tool) from each subject to enable ROI‐based quantitative R2* analyses. DAB‐enhanced histochemical iron stain (Meguro method), along with 6E10/4G8 immunohistochemistry, was used to identify iron‐positive Aβ deposits. Histological examination of neuroinflammation and microhemorrhages (Perls’ iron stain) was performed. T2‐w FLAIR images were acquired to assess the presence of ARIA‐E.ResultMGE imaging was capable of depicting brain pathology differences between three SQM age cohorts (ages 5, 16, 21). Absolute quantitation of R2* values, defined by ROI circumventing the cortex, revealed significant age‐related differences in selected brain regions, with the highest R2* counts detected in 21yr old monkeys. The ability to longitudinally track pathology‐related increase in R2* values was further validated by MRIs performed at specific intervals post‐initial scans in our geriatric monkeys. Iron‐positive Aβ deposits and microhemorrhages detected by MRI were confirmed via matched histological sections. Subsequent histological evaluation demonstrated disease‐stage differences in microgliosis and astrocytosis. Moreover, ARIA‐E like T2‐w signal hyperintensities were detected in our oldest cohort. Neuropathological correlates of ARIA‐E‐related changes were characterized histologically.ConclusionThe current study highlights the utility of MRI methodologies to monitor age‐dependent progression of Aβ‐related pathology, as well as the importance of the SQM model for future translational research on advancing therapeutic interventions targeting amyloid depositions.

In Vitro Validation of Regional Circumferential Strain Assessment in a Phantom Aortic Model Using Cine Displacement Encoding With Stimulated Echoes MRI.

A novel application of cine Displacement ENcoding with Stimulated Echoes Magnetic Resonance Imaging (DENSE MRI) has recently been described to assess regional heterogeneities in circumferential strain around the aortic wall in vivo; however, validation is first required for successful clinical translation. To validate the quantification of regional circumferential strain around the wall of an aortic phantom using DENSE MRI. In vitro phantom study. Three polyvinyl alcohol aortic phantoms with eight axially oriented nitinol wires embedded evenly around the walls. 3 T; gradient-echo aortic DENSE MRI with spiral cine readout, gradient-echo phase-contrast MRI (PCMR) with Cartesian cine readout. Phantoms were connected to a pulsatile flow loop and peak DENSE-derived regional circumferential Green strains at 16 equally spaced sectors around the wall were assessed according to previously published algorithms. "True" regional circumferential strains were calculated by manually tracking displacements of the nitinol wires by two independent observers. Normalized circumferential strains (NCS) were calculated by dividing regional strains by the mean strain. Finally, DENSE-derived regional strain was corrected by multiplying regional DENSE NCS by the mean strain calculated from the diameter change on the PCMR. One-sample t-test, Paired-sample t-test, and analysis of variance with Bonferroni correction, coefficient of variation (CoV), Bland-Altman analysis; P < 0.05 was considered statistically significant. Aortic DENSE MRI significantly overestimated circumferential strain compared to the wire-tracking method (mean difference and SD 0.030 ± 0.014, CoV 0.31). However, NCS demonstrated good agreement between DENSE and wire-tracking data (mean difference 0.000 ± 0.172, CoV 0.15). After correcting the DENSE-derived regional strain, the mean difference in regional circumferential strain between DENSE and wire-tracking was significantly reduced to 0.006 ± 0.008, and the CoV was reduced to 0.18. For aortic phantoms with mild spatial heterogeneity in circumferential strain, the previously published aortic DENSE MRI technique successfully assessed the regional NCS distribution but overestimated the mean strain. This overestimation is correctable by computing a more accurate mean circumferential strain using a separate cine scan. 2 TECHNICAL EFFICACY: Stage 2.

Decompose quantitative susceptibility mapping (QSM) to sub-voxel diamagnetic and paramagnetic components based on gradient-echo MRI data

PurposeA method named DECOMPOSE-QSM is developed to decompose bulk susceptibility measured with QSM into sub-voxel paramagnetic and diamagnetic components based on a three-pool complex signal model. MethodsMulti-echo gradient echo signal is modeled as a summation of three weighted exponentials corresponding to three types of susceptibility sources: reference susceptibility, diamagnetic and paramagnetic susceptibility relative to the reference. Paramagnetic component susceptibility (PCS) and diamagnetic component susceptibility (DCS) maps are constructed to represent the sub-voxel compartments by solving for linear and nonlinear parameters in the model. ResultsNumerical forward simulation and phantom validation confirmed the ability of DECOMPOSE-QSM to separate the mixture of paramagnetic and diamagnetic components. The PCS obtained from temperature-variant brainstem imaging follows the Curie's Law, which further validated the model and the solver. Initial in vivo investigation of human brain images showed the ability to extract sub-voxel PCS and DCS sources that produce visually enhanced contrast between brain structures comparing to threshold QSM.

Mapping magnetization transfer saturation (MTsat ) in human brain at 7T: Protocol optimization under specific absorption rate constraints.

To optimize a whole-brain magnetization transfer saturation (MTsat ) protocol at 7T, focusing on maximizing obtainable MTsat under the constraints of specific absorption rate (SAR) and transmit field inhomogeneity, while avoiding bias and keeping scan time short. MTsat is a semi-quantitative metric, obtained by spoiled gradient-echo MRI in the imaging steady-state. Optimization was based on an established 7T dual flip angle protocol, and focused on MT pulse, readout flip angle, repetition time (TR), offset frequency (Δ), and correction of residual effects from transmit field inhomogeneities by separate flip angle mapping. A 100% SAR level was reached at a 180° MT pulse flip angle, using a compact sinc main lobe (4 ms duration) and minimum TR = 26.5 ms. The use of Δ = +2.0 kHz caused no discernible direct saturation, while Δ = -2.0 kHz resulted in 45% higher MTsat in white matter (WM) compared to Δ = +2.0 kHz. A 4° readout flip angle eliminated bias while yielding a good signal-to-noise ratio. Increased TR yielded only a little increase in MTsat , and TR = 26.5 ms (scan time 04:58 min) was thus selected. Post hoc transmit field correction clearly improved homogeneity, especially in WM. The range of MTsat is limited at 7T, and this can partly be overcome by the exploitation of the asymmetry of the macromolecular lineshape through the sign of Δ. To reduce scan time, a compact MT pulse with a sufficiently narrow frequency response should be used. TR and readout flip angle should be kept short/small. Transmit field correction through separate flip angle mapping is required.

Cardiac-induced liver deformation as a measure of liver stiffness using dynamic imaging without magnetization tagging-preclinical proof-of-concept, clinical translation, reproducibility and feasibility in patients with cirrhosis.

MR elastography and magnetization-tagging use liver stiffness (LS) measurements to diagnose fibrosis but require physical drivers, specialist sequences and post-processing. Here we evaluate non-rigid registration of dynamic two-dimensional cine MRI images to measure cardiac-induced liver deformation (LD) as a measure of LS by (i) assessing preclinical proof-of-concept, (ii) clinical reproducibility and inter-reader variability, (iii) the effects of hepatic hemodynamic changes and (iv) feasibility in patients with cirrhosis. Sprague-Dawley rats (n = 21 bile duct ligated (BDL), n = 17 sham-operated controls) and fasted patients with liver cirrhosis (n = 11) and healthy volunteers (HVs, n = 10) underwent spoiled gradient-echo short-axis cardiac cine MRI studies at 9.4T (rodents) and 3.0T (humans). LD measurements were obtained from intrahepatic sub-cardiac regions-of-interest close to the diaphragmatic margin. One-week reproducibility and prandial stress induced hemodynamic changes were assessed in healthy volunteers. Normalized LD was higher in BDL (1.304 ± 0.062) compared with sham-operated rats (1.058 ± 0.045, P = 0.0031). HV seven-day reproducibility Bland-Altman (BA) limits-of-agreement (LoAs) were ± 0.028 a.u. and inter-reader variability BA LoAs were ± 0.030 a.u. Post-prandial LD increases were non-significant (+ 0.0083 ± 0.0076 a.u., P = 0.3028) and uncorrelated with PV flow changes (r = 0.42, p = 0.2219). LD measurements successfully obtained from all patients were not significantly higher in cirrhotics (0.102 ± 0.0099 a.u.) compared with HVs (0.080 ± 0.0063 a.u., P = 0.0847). Cardiac-induced LD is a conceptually reasonable approach from preclinical studies, measurements demonstrate good reproducibility and inter-reader variability, are less likely to be affected by hepatic hemodynamic changes and are feasible in patients with cirrhosis.

Coronal Gradient Echo MRI to Visualize the Zona Incerta for Deep Brain Stimulation Targeting in Parkinson’s Disease

Introduction: Deep brain stimulation of the zona incerta is effective at treating tremor and other forms of parkinsonism. However, the structure is not well visualized with standard MRI protocols making direct surgical targeting unfeasible and contributing to inconsistent clinical outcomes. In this study, we applied coronal gradient echo MRI to directly visualize the rostral zona incerta in Parkinson’s disease patients to improve targeting for deep brain stimulation. Methods: We conducted a prospective study to optimize and evaluate an MRI sequence to visualize the rostral zona incerta in patients with Parkinson’s disease (n = 31) and other movement disorders (n = 13). We performed a contrast-to-noise ratio analysis of specific regions of interest to quantitatively assess visual discrimination of relevant deep brain structures in the optimized MRI sequence. Regions of interest were independently assessed by 2 neuroradiologists, and interrater reliability was assessed. Results: Rostral zona incerta and subthalamic nucleus were well delineated in our 5.5-min MRI sequence, indicated by excellent interrater agreement between neuroradiologists for region-of-interest measurements (>0.90 intraclass coefficient). Mean contrast-to-noise ratio was high for both rostral zona incerta (6.39 ± 3.37) and subthalamic nucleus (17.27 ± 5.61) relative to adjacent white matter. There was no significant difference between mean signal intensities or contrast-to-noise ratio for Parkinson’s and non-Parkinson’s patients for either structure. Discussion/Conclusion: Our optimized coronal gradient echo MRI sequence delineates subcortical structures relevant to traditional and novel deep brain stimulation targets, including the zona incerta, with high contrast-to-noise. Future studies will prospectively apply this sequence to surgical planning and postimplantation outcomes.

Test-retest reliability and smallest detectable change (SDC) of MRI-based cartilage thickness analysis in a large multicenter randomized controlled clinical trial of knee osteoarthritis

Test-retest reliability and smallest detectable change (SDC) of MRI-based cartilage thickness analysis in a large multicenter randomized controlled clinical trial of knee osteoarthritis

Magnetization-prepared 2 Rapid Gradient-Echo MRI for B1 Insensitive 3D T1 Mapping of Hip Cartilage: An Experimental and Clinical Validation.

Background Often used for T1 mapping of hip cartilage, three-dimensional (3D) dual-flip-angle (DFA) techniques are highly sensitive to flip angle variations related to B1 inhomogeneities. The authors hypothesized that 3D magnetization-prepared 2 rapid gradient-echo (MP2RAGE) MRI would help provide more accurate T1 mapping of hip cartilage at 3.0 T than would 3D DFA techniques. Purpose To compare 3D MP2RAGE MRI with 3D DFA techniques using two-dimensional (2D) inversion recovery T1 mapping as a standard of reference for hip cartilage T1 mapping in phantoms, healthy volunteers, and participants with hip pain. Materials and Methods T1 mapping at 3.0 T was performed in phantoms and in healthy volunteers using 3D MP2RAGE MRI and 3D DFA techniques with B1 field mapping for flip angle correction. Participants with hip pain prospectively (July 2019-January 2020) underwent indirect MR arthrography (with intravenous administration of 0.2 mmol/kg of gadoterate meglumine), including 3D MP2RAGE MRI. A 2D inversion recovery-based sequence served as a T1 reference in phantoms and in participants with hip pain. In healthy volunteers, cartilage T1 was compared between 3D MP2RAGE MRI and 3D DFA techniques. Paired t tests and Bland-Altman analysis were performed. Results Eleven phantoms, 10 healthy volunteers (median age, 27 years; range, 26-30 years; five men), and 20 participants with hip pain (mean age, 34 years ± 10 [standard deviation]; 17 women) were evaluated. In phantoms, T1 bias from 2D inversion recovery was lower for 3D MP2RAGE MRI than for 3D DFA techniques (mean, 3 msec ± 11 vs 253 msec ± 85; P < .001), and, unlike 3D DFA techniques, the deviation found with MP2RAGE MRI did not correlate with increasing B1 deviation. In healthy volunteers, regional cartilage T1 difference (109 msec ± 163; P = .008) was observed only for the 3D DFA technique. In participants with hip pain, the mean T1 bias of 3D MP2RAGE MRI from 2D inversion recovery was -23 msec ± 31 (P < .001). Conclusion Compared with three-dimensional (3D) dual-flip-angle techniques, 3D magnetization-prepared 2 rapid gradient-echo MRI enabled more accurate T1 mapping of hip cartilage, was less affected by B1 inhomogeneities, and showed high accuracy against a T1 reference in participants with hip pain. © RSNA, 2021.

Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease.

ObjectiveTo investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we longitudinally evaluated families with dominantly inherited Alzheimer disease (DIAD).MethodsMutation carriers (n = 310) and noncarriers (n = 201) underwent neuroimaging, including gradient echo MRI sequences to detect CMHs, and neuropsychological and clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical markers of disease.ResultsThree percent of noncarriers and 8% of carriers developed CMHs primarily located in lobar areas. Carriers with CMHs were older, had higher diastolic blood pressure and Hachinski ischemic scores, and more clinical, cognitive, and motor impairments than those without CMHs. APOE ε4 status was not associated with the prevalence or incidence of CMHs. Prevalent or incident CMHs predicted faster change in Clinical Dementia Rating although not composite cognitive measure, cortical thickness, hippocampal volume, or white matter lesions. Critically, the presence of 2 or more CMHs was associated with a significant risk for development of additional CMHs over time (8.95 ± 10.04 per year).ConclusionOur study highlights factors associated with the development of CMHs in individuals with DIAD. CMHs are a part of the underlying disease process in DIAD and are significantly associated with dementia. This highlights that in participants in treatment trials exposed to drugs, which carry the risk of ARIA-H as a complication, it may be challenging to separate natural incidence of CMHs from drug-related CMHs.

CT-like images based on T1 spoiled gradient-echo and ultra-short echo time MRI sequences for the assessment of vertebral fractures and degenerative bone changes of the spine

ObjectivesTo evaluate the performance of 3D T1w spoiled gradient-echo (T1SGRE) and ultra-short echo time (UTE) MRI sequences for the detection and assessment of vertebral fractures and degenerative bone changes compared with conventional CT.MethodsFractures (n = 44) and degenerative changes (n = 60 spinal segments) were evaluated in 30 patients (65 ± 14 years, 18 women) on CT and 3-T MRI, including CT-like images derived from T1SGRE and UTE. Two radiologists evaluated morphological features on both modalities: Genant and AO/Magerl classifications, anterior/posterior vertebral height, fracture age; disc height, neuroforaminal diameter, grades of spondylolisthesis, osteophytes, sclerosis, and facet joint degeneration. Diagnostic accuracy and agreement between MRI and CT and between radiologists were assessed using crosstabs, weighted κ, and intraclass correlation coefficients. Image quality was graded on a Likert scale.ResultsFor fracture detection, sensitivity, specificity, and accuracy were 0.95, 0.98, and 0.97 for T1SGRE and 0.91, 0.96, and 0.95 for UTE. Agreement between T1SGRE and CT was substantial to excellent (e.g., Genant: κ, 0.92 [95% confidence interval, 0.83–1.00]; AO/Magerl: κ, 0.90 [0.76–1.00]; osteophytes: κ, 0.91 [0.82–1.00]; sclerosis: κ, 0.68 [0.48–0.88]; spondylolisthesis: ICCs, 0.99 [0.99–1.00]). Agreement between UTE and CT was lower, ranging from moderate (e.g., sclerosis: κ, 0.43 [0.26–0.60]) to excellent (spondylolisthesis: ICC, 0.99 [0.99–1.00]). Inter-reader agreement was substantial to excellent (0.52–1.00), respectively, for all parameters. Median image quality of T1SGRE was rated significantly higher than that of UTE (p < 0.001).ConclusionsMorphologic assessment of bone pathologies of the spine using MRI was feasible and comparable to CT, with T1SGRE being more robust than UTE.Key Points• Vertebral fractures and degenerative bone changes can be assessed on CT-like MR images, with 3D T1w spoiled gradient-echo–based images showing a high diagnostic accuracy and agreement with CT.• This could enable MRI to precisely assess bone morphology, and 3D T1SGRE MRI sequences may substitute additional spinal CT examinations in the future.• Image quality and robustness of T1SGRE sequences are higher than those of UTE MRI for the assessment of bone structures.

Melittin-loaded Iron Oxide Nanoparticles Prevent Intracranial Arterial Dolichoectasia Development through Inhibition of Macrophage-mediated Inflammation

Rationale: In intracranial arterial dolichoectasia (IADE) development, the feedback loop between inflammatory cytokines and macrophages involves TNF-α and NF-κB signaling pathways and leads to subsequent MMP-9 activation and extracellular matrix (ECM) degeneration. In this proof-of-concept study, melittin-loaded L-arginine-coated iron oxide nanoparticle (MeLioN) was proposed as the protective measure of IADE formation for this macrophage-mediated inflammation and ECM degeneration.Methods: IADE was created in 8-week-old C57BL/6J male mice by inducing hypertension and elastase injection into a basal cistern. Melittin was loaded on the surface of ION as a core-shell structure (hydrodynamic size, 202.4 nm; polydispersity index, 0.158). Treatment of MeLioN (2.5 mg/kg, five doses) started after the IADE induction, and the brain was harvested in the third week. In the healthy control, disease control, and MeLioN-treated group, the morphologic changes of the cerebral arterial wall were measured by diameter, thickness, and ECM composition. The expression level of MMP-9, CD68, MCP-1, TNF-α, and NF-κB was assessed from immunohistochemistry, polymerase chain reaction, and Western blot assay.Results: MeLioN prevented morphologic changes of cerebral arterial wall related to IADE formation by restoring ECM alterations and suppressing MMP-9 expression. MeLioN inhibited MCP-1 expression and reduced CD68-positive macrophage recruitments into cerebral arterial walls. MeLioN blocked TNF-α activation and NF-κB signaling pathway. In the Sylvian cistern, co-localization was found between the CD68-positive macrophage infiltrations and the MeLioN distributions detected on Prussian Blue and T2* gradient-echo MRI, suggesting the role of macrophage harboring MeLioN.Conclusions: The macrophage infiltration into the arterial wall plays a critical role in the MMP-9 secretion. MeLioN, designed for ION-mediated melittin delivery, effectively prevents IADE formation by suppressing macrophage-mediated inflammations and MMP activity. MeLioN can be a promising strategy preventing IADE development in high-risk populations.

Magnetic resonance imaging-based synthetic computed tomography of the lumbar spine for surgical planning: a clinical proof-of-concept.

Computed tomography scanning of the lumbar spine incurs a radiation dose ranging from 3.5 mSv to 19.5 mSv as well as relevant costs and is commonly necessary for spinal neuronavigation. Mitigation of the need for treatment-planning CT scans in the presence of MRI facilitated by MRI-based synthetic CT (sCT) would revolutionize navigated lumbar spine surgery. The authors aim to demonstrate, as a proof of concept, the capability of deep learning-based generation of sCT scans from MRI of the lumbar spine in 3 cases and to evaluate the potential of sCT for surgical planning. Synthetic CT reconstructions were made using a prototype version of the "BoneMRI" software. This deep learning-based image synthesis method relies on a convolutional neural network trained on paired MRI-CT data. A specific but generally available 4-minute 3D radiofrequency-spoiled T1-weighted multiple gradient echo MRI sequence was supplemented to a 1.5T lumbar spine MRI acquisition protocol. In the 3 presented cases, the prototype sCT method allowed voxel-wise radiodensity estimation from MRI, resulting in qualitatively adequate CT images of the lumbar spine based on visual inspection. Normal as well as pathological structures were reliably visualized. In the first case, in which a spiral CT scan was available as a control, a volume CT dose index (CTDIvol) of 12.9 mGy could thus have been avoided. Pedicle screw trajectories and screw thickness were estimable based on sCT findings. The evaluated prototype BoneMRI method enables generation of sCT scans from MRI images with only minor changes in the acquisition protocol, with a potential to reduce workflow complexity, radiation exposure, and costs. The quality of the generated CT scans was adequate based on visual inspection and could potentially be used for surgical planning, intraoperative neuronavigation, or for diagnostic purposes in an adjunctive manner.

Dysfunction of the Blood-brain Barrier in Cerebral Microbleeds: from Bedside to Bench.

Cerebral microbleeds (CMBs) are a disorder of cerebral microvessels that are characterized as small (<10 mm), hypointense, round or ovoid lesions seen on T2*-weighted gradient echo MRI. There is a high prevalence of CMBs in community-dwelling healthy older people. An increasing number of studies have demonstrated the significance of CMBs in stroke, dementia, Parkinson’s disease, gait disturbances and late-life depression. Blood-brain barrier (BBB) dysfunction is considered to be the event that initializes CMBs development. However, the pathogenesis of CMBs has not yet been clearly elucidated. In this review, we introduce the pathogenesis of CMBs, hypertensive vasculopathy and cerebral amyloid angiopathy, and review recent research that has advanced our understanding of the mechanisms underlying BBB dysfunction and CMBs presence. CMBs-associated risk factors can exacerbate BBB breakdown through the vulnerability of BBB anatomical and functional changes. Finally, we discuss potential pharmacological approaches to target the BBB as therapy for CMBs.

Early assessment of knee osteoarthritis using three-dimensional water-selective gradient-echo MRI technique

ObjectiveThe aim was to evaluate the role of three-dimensional water-selective gradient-echo MRI technique (WATS) in early assessment of knee osteoarthritis (OA).BackgroundOA is a degenerative joint disease occurring in older adults. The 3D WATS is the best imaging technique currently available for the assessment of articular cartilage.Patients and methodsA prospective study was conducted on 25 patients with suspected knee joint disorder who were enrolled from the Rheumatology and Orthopedic Departments in Mansoura University Hospitals and Outpatient Clinic in Menoufia University Hospital from February 2017 to February 2018. Complete history, clinical examination, and imaging analysis using a knee coil in a 1.5T MRI scanner were done.ResultsWomen were more affected with OA (68%) than men (32%). Cartilage defects were the most common MRI finding (76%). Osteophyte formation is represented by 12 (48%) cases. There were six cases with normal cartilage appearance and 19 cases have different grades of cartilage defect. Grade II cartilage defect was the most common finding (eight cases, 32%); 12 (48%) cases presented with osteophyte; 11 (44%) cases had osteophytes greater than 5 mm and one (4%) case had osteophyte of less than 5 mm.ConclusionThree-dimensional Gradient echo imaging is considered the standard technique for morphologic evaluations of knee cartilage. The 3D-WATS are proved to be more helpful in accurate assessment of cartilage thickness and volume, showing morphological changes of cartilage surface and internal cartilage signal changes. The 3D-WATS sequences cannot replace routine 2D sequences because they do not allow accurate assessment of other important joint structures.

Multi-compartment analysis of the complex gradient-echo signal quantifies myelin breakdown in premanifest Huntington's disease

White matter (WM) alterations have been identified as a relevant pathological feature of Huntington’s disease (HD). Increasing evidence suggests that WM changes in this disorder are due to alterations in myelin‐associated biological processes. Multi-compartmental analysis of the complex gradient-echo MRI signal evolution in WM has been shown to quantify myelin in vivo, therefore pointing to the potential of this technique for the study of WM myelin changes in health and disease. This study first characterized the reproducibility of metrics derived from the complex multi-echo gradient-recalled echo (mGRE) signal across the corpus callosum in healthy participants, finding highest reproducibility in the posterior callosal segment. Subsequently, the same analysis pipeline was applied in this callosal region in a sample of premanifest HD patients (n = 19) and age, sex and education matched healthy controls (n = 21). In particular, we focused on two myelin-associated derivatives: i. the myelin water signal fraction (fm), a parameter dependent on myelin content; and ii. The difference in frequency between myelin and intra-axonal water pools (Δω), a parameter dependent on the ratio between the inner and the outer axonal radii. fm was found to be lower in HD patients (β = −0.13, p = 0.03), while Δω did not show a group effect. Performance in tests of working memory, executive function, social cognition and movement was also assessed, and a greater age-related decline in executive function was detected in HD patients (β = −0.06, p = 0.006), replicating previous evidence of executive dysfunction in HD. Finally, the correlation between fm, executive function, and proximity to disease onset was explored in patients, and a positive correlation between executive function and fm was detected (r = 0.542; p = 0.02). This study emphasises the potential of complex mGRE signal analysis for aiding understanding of HD pathogenesis and progression. Moreover, expanding on evidence from pathology and animal studies, it provides novel in vivo evidence supporting myelin breakdown as an early feature of HD.

Neuropathological correlates of cortical superficial siderosis in cerebral amyloid angiopathy

AbstractBackgroundCortical superficial siderosis (cSS) is an established hemorrhagic neuroimaging marker of cerebral amyloid angiopathy (CAA) and emerging as a strong independent risk factor for future lobar intracerebral hemorrhage. However, the underlying neuropathological correlates and pathophysiological mechanisms of cSS remain elusive.MethodFourteen autopsy cases with CAA (mean age at death 73 years, 9 males) and three controls (mean age at death 91 years, 1 male) were included. Intact formalin‐fixed cerebral hemispheres were scanned on a 3 tesla MRI scanner. cSS was assessed on ex vivo gradient echo and turbo spin echo MRI sequences and compared to findings on available in vivo MRI. Subsequently, eleven representative areas in four cases with available in vivo MRI scans were sampled for histopathological verification of MRI‐defined cSS. In addition, samples were taken from pre‐defined standard areas of the brain, blinded to MRI findings. Serial sections were stained for H&amp;E and Perls’ Prussian blue, and immunohistochemistry was performed against Aβ and GFAP.ResultcSS was present on ex vivo MRI in 8/14 cases and 0/3 controls. Histopathologically, cSS corresponded to Iron‐positive hemosiderin deposits in the subarachnoid space and superficial cortical layers, indicative of chronic bleeding events originating from the leptomeningeal vessels (Figure 1). Increased severity of cSS was associated with upregulation of reactive astrocytes. Next, cSS and CAA pathology were assessed on a total of 65 sections from MRI‐targeted and untargeted samples. Moderate‐to‐severe cSS was associated with concentric splitting (an advanced form of CAA‐related vascular damage) of the walls of leptomeningeal vessels (p&lt;0.0001), but reduced CAA severity in cortical vessels (p=0.048). Moderate‐to‐severe cSS was associated with the presence of microinfarcts (p=0.025), though not microbleeds (p=0.973).ConclusioncSS on MRI corresponds to Iron‐positive depositions in the superficial cortical layers, representing the chronic manifestation of bleeding episodes from leptomeningeal vessels. cSS appears to be the result predominantly of advanced CAA of the leptomeningeal vessels and may trigger secondary ischemic injury in affected areas.

Dixon or DWI – Comparing the utility of fat fraction and apparent diffusion coefficient to distinguish between malignant and acute osteoporotic vertebral fractures

PurposeTo compare fat fraction (FF) and apparent diffusion coefficient (ADC) as discriminators distinguishing malignant from acute/subacute osteoporotic vertebral fractures. Method1.5 T MRIs of 42 malignant and 27 acute/subacute osteoporotic vertebral fractures (38 patients) were retrospectively reviewed. Two readers independently classified fractures as malignant or osteoporotic based on conventional imaging morphology. Diagnostic reader confidence was rated as confident or not confident. FF was derived from axial T1 gradient-echo 2-point Dixon MRI. ADC maps were calculated from axial b50 and b900 images. Both readers independently performed ROI measurements of mean FF and ADC of the same fractured vertebrae. FF and ADC values, corresponding ROC curves and optimized cut-off value performance were compared. Inter-reader agreement was analysed by calculation of intraclass correlation coefficients (ICCs). A p-value < 0.05 was deemed significant. ResultsMean FF and ADC were significantly lower in malignant (9.5 % and 1.05 × 10−3 mm²/s) compared to osteoporotic fractures (32 % and 1.34 × 10−3 mm²/s, all p < 0.001). The optimal cut-off FF was 11.5 %, detecting malignant fractures with 86 %/89 % sensitivity/specificity. The optimal ADC cut-off of 1.04 × 10−3 mm/s² yielded 62 %/96 % sensitivity/specificity. FF AUC (0.93) was significantly larger than ADC AUC (0.82, p = 0.03). In the subgroup of nine cases reported with low expert reader confidence, the optimized cut-off specificities of FF (83 %) and ADC (83 %) exceeded reader specificity (50 %). There was excellent inter-reader agreement for mean FF (ICC = 0.99) and good agreement for mean ADC (ICC = 0.86) measurements. ConclusionFF and ADC can improve reader specificity to distinguish between malignant and acute or subacute osteoporotic vertebral fractures. As single discriminator, FF was superior to ADC.

PREDICTIVE FACTORS OF HEMORRHAGIC ISCHEMIC STROKE DETECTED BY CT AND MRI GRADIENT-ECHO T2 WEIGHTED IMAGE (GRE)

Background: Risk of hemorrhage is significantly increased in large infarcts, with mass effect supporting the importance of edema for tissue damage and the deleterious effect of late reperfusion when edema resolves. In some instances, the rupture of the vascular wall secondary to ischemia-induced endothelial necrosis might cause an intra-infarct hematoma. Vascular rupture can explain very early hemorrhagic infarcts and early intra infarct hematoma (between 6 and 18 hours after stroke), whereas hemorrhagic transformation usually develops within 48 hours to 2 weeks. Intra cerebral hemorrhage (ICH) occurs as a result of bleeding from an arterial source directly into the brain parenchyma and accounts for 5–15% of all strokes. Objective: The aim of this study was to determine the predictive factors of hemorrhagic transformation in patient with acute ischemic stroke detected by brain CT and MRI gradient echo T2 weighted image (GRE). Patients and Methods: This was a cross sectional randomized prospective study carried out on 60 patients (32 males and 28 females), admitted at Neurology Department and Stroke Unit of Mostafa Kamel Military Hospital, within the first 24 hours of their symptoms. The study was carried out during the period from 1st of January 2018 till the end of December 2018. Results: The results of this study showed that the size of infarction was small in 27 (45.0%) patients and large in 33 (55.0%) patients, the micro bleeds were found in 32 (53.3%) of the studied patients, and the hemorrhagic transformation was found in 11 (18.3%) of the patients. The results showed that there was a significant relation between micro bleeds and hypertension, diabetes mellitus, dyslipidemia, past history of stroke, cardiac disease and hemorrhagic transformation. The small size infarction showed a higher percent of micro bleeds. Regarding the hemorrhagic transformation, the risk factors were the size of infarction, anticoagulant use, hypertension, diabetic and cardiac diseases. Conclusion: The most predictive factors of hemorrhagic transformation was the size of infarction (higher in large), micro bleed, anticoagulant use, hypertension, dyslipidemia and cardiac disease, while the most predictive factors of micro bleeds were the size of infarction (higher in small), age, hypertension, dyslipidemia, past history of stroke, diabetes mellitus, and cardiac disease.