UNASSIGNED: We aimed to investigate whether combined phosphorous (31P) magnetic resonance spectroscopic imaging (MRSI) and quantitative T 2 \' mapping are able to detect alterations of the cerebral oxygen extraction fraction (OEF) and intracellular pH (pHi) as markers the of cellular energy metabolism in cerebral small vessel disease (SVD).
UNASSIGNED: 32 patients with SVD and 17 age-matched healthy control subjects were examined with 3-dimensional 31P MRSI and oxygenation-sensitive quantitative T 2 \' mapping (1/ T 2 \'  = 1/T2* - 1/T2) at 3 Tesla (T). PHi was measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative T 2 \' values were averaged across the entire white matter (WM). Furthermore, T 2 \' values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls.
UNASSIGNED: Quantitative T 2 \' values were significantly increased across the entire WM and in the NAWM in patients compared to control subjects (149.51 ± 16.94 vs. 138.19 ± 12.66 ms and 147.45 ± 18.14 vs. 137.99 ± 12.19 ms, p < 0.05). WM T 2 \' values correlated significantly with the WMH load (ρ=0.441, p = 0.006). Increased T 2 \' was significantly associated with more alkaline pHi (ρ=0.299, p < 0.05). Both T 2 \' and pHi were significantly positively correlated with vascular pulsatility in the distal carotid arteries (ρ=0.596, p = 0.001 and ρ=0.452, p = 0.016).
UNASSIGNED: This exploratory study found evidence of impaired cerebral OEF in SVD, which is associated with intracellular alkalosis as an adaptive mechanism. The employed techniques provide new insights into the pathophysiology of SVD with regard to disease-related consequences on the cellular metabolic state.

UNASSIGNED: Cerebral small vessel diseases (SVDs) are a major cause of stroke and dementia. Yet, specific treatment strategies are lacking in part because of a limited understanding of the underlying disease processes. There is therefore an urgent need to study SVDs at their core, the small vessels themselves.
UNASSIGNED: This paper presents the rationale and design of the ZOOM@SVDs study, which aims to establish measures of cerebral small vessel dysfunction on 7T MRI as novel disease markers of SVDs.
UNASSIGNED: ZOOM@SVDs is a prospective observational cohort study with two years follow-up. ZOOM@SVDs recruits participants with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL, N = 20), sporadic SVDs (N = 60), and healthy controls (N = 40). Participants undergo 7T brain MRI to assess different aspects of small vessel function including small vessel reactivity, cerebral perforating artery flow, and pulsatility. Extensive work-up at baseline and follow-up further includes clinical and neuropsychological assessment as well as 3T brain MRI to assess conventional SVD imaging markers. Measures of small vessel dysfunction are compared between patients and controls, and related to the severity of clinical and conventional MRI manifestations of SVDs.
UNASSIGNED: ZOOM@SVDs will deliver novel markers of cerebral small vessel function in patients with monogenic and sporadic forms of SVDs, and establish their relation with disease burden and progression. These small vessel markers can support etiological studies in SVDs and may serve as surrogate outcome measures in future clinical trials to show target engagement of drugs directed at the small vessels.

Detection of incipient cognitive impairment and dementia pathophysiology is critical to identify preclinical populations and target potentially disease modifying interventions towards them. There are currently concerted efforts for such detection for Alzheimer\'s disease (AD). By contrast, the examination of cognitive markers and their relationship to biomarkers for Vascular Cognitive Impairment (VCI) is far less established, despite VCI being highly prevalent and often concomitantly presenting with AD. Critically, vascular risk factors are currently associated with the most viable treatment options via pharmacological and non-pharmacological intervention, hence early identification of vascular factors have important implications for modifying dementia disease trajectories. The aim of this review is to examine the current evidence of cognitive marker correlates to VCI pathology. We begin by examining midlife risk factors that predict VCI. Next, discuss preclinical cognitive hallmarks of VCI informed by insights from neuropsychological assessment, network connectivity and ERP/EEG experimental findings. Finally, we discuss limitations of current cognitive assessments and the need for future cognitive test development to inform diagnostic assessment. As well as, intervention outcome measures for preclinical VCI. In turn, these tests will inform earlier detection of vascular changes and allow implementation of disease intervention approaches.

Spinal cord injuries pose grave medical and socioeconomic burdens warranting measures for early diagnosis, triaging, prognostication and therapeutics. Imaging has since long played a pivotal role in this regard, with continuing research and technological advancements opening newer frontiers. One such advanced Magnetic resonance (MR) technique is Diffusion tensor imaging (DTI) which assesses cord microstructure by tracking the movement of water molecules in biological tissues. DTI utilizes the principle of anisotropy exhibited by the normal compact white matter (WM) tracts of the cord, in which direction-dependent water molecular motion is seen along the axonal axis. Disruption of this complex structure in response to injury alters the movement of these molecules, interrupting anisotropy and thereby DTI metrics. Evaluation of DTI images can be done both by quantitative indices, of which fractional anisotropy (FA) and mean diffusivity (MD) are the most commonly used and by qualitative fiber tracking (tractography) methods in which three-dimensional WM tracts are reconstructed by algorithmic post-processing. Reduced FA is consistently seen at injury sites as a direct consequence of disturbance of anisotropy. Diffusivity values are however more variable with both high and low values recorded across studies. 3D tractography images allow visual assessment of cord integrity, morphology, and orientation. Significant correlation is found between DTI parameters and various spinal injury scores. Furthermore, DTI also helps in accurate lesion mapping and in assessing cord changes distant from injury epicenter providing a holistic evaluation. From its inception, consistent progress in the understanding and application of DTI has effectuated its clinical utility and impact. Incorporation into day-to-day diagnostics is however still challenging, due to suboptimal image acquisition, difficult post-processing, and lack of standardized protocols & image interpretation guidelines. Further research with technical validation, development of normative and disease data sets, and histological confirmation will help establish this novel technique in routine diagnostics.

BACKGROUND: Posterior fossa tumors represent two thirds of brain tumors in children. Although progress in treatment has improved survival rates over the past few years, long-term memory impairments in survivors are frequent and have an impact on academic achievement. The hippocampi, cerebellum and cerebellar-cortical networks play a role in several memory systems. They are affected not only by the location of the tumor itself and its surgical removal, but also by the supratentorial effects of complementary treatments, particularly radiotherapy. The IMPALA study will investigate the impact of irradiation doses on brain structures involved in memory, especially the hippocampi and cerebellum.
METHODS: In this single-center prospective behavioral and neuro-imaging study, 90 participants will be enrolled in three groups. The first two groups will include patients who underwent surgery for a posterior fossa brain tumor in childhood, who are considered to be cured, and who completed treatment at least 5 years earlier, either with radiotherapy (aggressive brain tumor; Group 1) or without (low-grade brain tumor; Group 2). Group 3 will include control participants matched with Group 1 for age, sex, and handedness. All participants will perform an extensive battery of neuropsychological tests, including an assessment of the main memory systems, and undergo multimodal 3 T MRI. The irradiation dose to the different brain structures involved in memory will be collected from the initial radiotherapy dosimetry.
CONCLUSIONS: This study will provide long-term neuropsychological data about four different memory systems (working memory, episodic memory, semantic memory, and procedural memory) and the cognitive functions (attention, language, executive functions) that can interfere with them, in order to better characterize memory deficits among the survivors of brain tumors. We will investigate the correlations between neuropsychological and neuroimaging data on the structural (3DT1), microstructural (DTI), functional (rs-fMRI), vascular (ASL) and metabolic (spectroscopy) impact of the tumor and irradiation dose. This study will thus inform the setting of dose constraints to spare regions linked to the development of cognitive and memory functions.
BACKGROUND: ClinicalTrials.gov: NCT04324450, registered March 27, 2020, updated January 25th, 2021. Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT04324450.

For magnetic resonance imaging (MRI) of non-traumatic brachial plexus (BP) lesions, sequences with contrast injection should be considered in the differentiation between tumors, infection, postoperative conditions, and post-radiation changes. The most common non-traumatic inflammatory BP neuropathy is radiation neuropathy. T2-weighted images may help to distinguish neoplastic infiltration showing a high signal from radiation-induced neuropathy with fibrosis presenting a low signal. MRI findings in inflammatory BP neuropathy are usually absent or discrete. Diffuse edema of the BP localized mainly in the supraclavicular part of BP, with side-to-side differences, and shoulder muscle denervation may be found on MRI. BP infection is caused by direct infiltration from septic arthritis of the shoulder joint, spondylodiscitis, or lung empyema. MRI may help to narrow down the list of differential diagnoses of tumors. The most common tumor of BP is metastasis. The most common primary tumor of BP is neurofibroma, which is visible as fusiform thickening of a nerve. In its solitary state, it may be challenging to differentiate from a schwannoma. The most common MRI finding is a neurogenic variant of thoracic outlet syndrome with an asymmetry of signal and thickness of the BP with edema. In abduction, a loss of fat directly related to the BP may be seen. Diffusion tensor imaging is a promising novel MRI sequences; however, the small diameter of the nerves contributing to the BP and susceptibility to artifacts may be challenging in obtaining sufficiently high-quality images.

Since its approval in treating a number of movement disorders, magnetic resonance imaging-guided focused ultrasound (MRgFUS) has been adopted rapidly as one of the standard treatment modalities internationally. However, the efficiency of the energy delivered by the ultrasonic waves is largely determined by the highly variable bone morphology and density characteristics of the skull. One of the widely accepted indices used to facilitate patient selection is the skull density ratio (SDR). Earlier literature suggested that an SDR of less than 0.4 would be unfavorable for MRgFUS treatment. Some prior studies have excluded patients with hyperostosis. However, there is little published data regarding the impact of other skull features such as hyperostosis on treatment success. We present the case of a 66-year-old man with medically refractory essential tremor who had an SDR of 0.38 and extensive hyperostosis frontalis interna and underwent attempted MRgFUS thalamotomy treatment. However, intraoperatively the treatment was unsuccessful in generating sufficiently elevated temperature to create a lesion of the usual desired volume, and as expected, there was minimal clinical improvement. For comparison, we also summarize a case series of 4 other patients with an SDR of less than 0.4 who had successful outcomes. We believe that SDR should not be used as the only means of selecting patients for MRgFUS. Instead, important factors such as hyperostosis should be taken into consideration for patient selection and pretreatment counseling.

UNASSIGNED: The absolute number of new stroke patients is annually increasing and there still remains only a few Food and Drug Administration (FDA) approved treatments with significant limitations available to patients. Tanshinone IIA (Tan IIA) is a promising potential therapeutic for ischemic stroke that has shown success in pre-clinical rodent studies but lead to inconsistent efficacy results in human patients. The physical properties of Tan-IIA, including short half-life and low solubility, suggests that Poly (lactic-co-glycolic acid) (PLGA) nanoparticle-assisted delivery may lead to improve bioavailability and therapeutic efficacy. The objective of this study was to develop Tan IIA-loaded nanoparticles (Tan IIA-NPs) and to evaluate their therapeutic effects on cerebral pathological changes and consequent motor function deficits in a pig ischemic stroke model.
UNASSIGNED: Tan IIA-NP treated neural stem cells showed a reduction in SOD activity in in vitro assays demonstrating antioxidative effects. Ischemic stroke pigs treated with Tan IIA-NPs showed reduced hemispheric swelling when compared to vehicle only treated pigs (7.85 ± 1.41 vs. 16.83 ± 0.62%), consequent midline shift (MLS) (1.72 ± 0.07 vs. 2.91 ± 0.36 mm), and ischemic lesion volumes (9.54 ± 5.06 vs. 12.01 ± 0.17 cm3) when compared to vehicle-only treated pigs. Treatment also lead to lower reductions in diffusivity (-37.30 ± 3.67 vs. -46.33 ± 0.73%) and white matter integrity (-19.66 ± 5.58 vs. -30.11 ± 1.19%) as well as reduced hemorrhage (0.85 ± 0.15 vs 2.91 ± 0.84 cm3) 24 h post-ischemic stroke. In addition, Tan IIA-NPs led to a reduced percentage of circulating band neutrophils at 12 (7.75 ± 1.93 vs. 14.00 ± 1.73%) and 24 (4.25 ± 0.48 vs 5.75 ± 0.85%) hours post-stroke suggesting a mitigated inflammatory response. Moreover, spatiotemporal gait deficits including cadence, cycle time, step time, swing percent of cycle, stride length, and changes in relative mean pressure were less severe post-stroke in Tan IIA-NP treated pigs relative to control pigs.
UNASSIGNED: The findings of this proof of concept study strongly suggest that administration of Tan IIA-NPs in the acute phase post-stroke mitigates neural injury likely through limiting free radical formation, thus leading to less severe gait deficits in a translational pig ischemic stroke model. With stroke as one of the leading causes of functional disability in the United States, and gait deficits being a major component, these promising results suggest that acute Tan IIA-NP administration may improve functional outcomes and the quality of life of many future stroke patients.

UNASSIGNED: To investigate the relationship between bimanual performance deficits measured using kinematics and callosum (CC) white matter changes that occur in people with chronic stroke.
UNASSIGNED: Cross-sectional, observational study of participants with chronic stroke and age-matched controls.
UNASSIGNED: Recruitment and assessments occurred at a stroke recovery research center. Behavioral assessments were performed in a controlled laboratory setting. Magnetic resonance imaging scans were performed at the Center for Biomedical Imaging.
UNASSIGNED: Individuals were enrolled and completed the study (N=39; 21 participants with chronic stroke; 18 age-matched controls with at least 2 stroke risk factors).
UNASSIGNED: Diffusion imaging metrics were obtained for each individual\'s CC and corticospinal tract (CST), including mean kurtosis (MK) and fractional anisotropy (FA). A battery of motor assessments, including bimanual kinematics, were collected from individuals while performing bimanual reaching.
UNASSIGNED: Participants with stroke had lower FA and MK in the CST of the lesioned hemisphere when compared with the non-lesioned hemisphere. The FA and MK values in the CST were correlated with measures of unimanual hand performance. In addition, participants with stroke had significantly lower FA and MK in the CC than matched controls. CC diffusion metrics positively correlated with hand asymmetry and trunk displacement during bimanual performance, even when correcting for age and lesion volume.
UNASSIGNED: These data confirm previous studies that linked CST integrity to unimanual performance and provide new data demonstrating a link between CC integrity and both bimanual motor deficits and compensatory movements.

BACKGROUND: Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2.
METHODS: In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information.
RESULTS: In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl\'s gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected p value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl\'s gyrus, and Global MD of WM were found to correlate with memory loss (p value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss (p value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level (p value <0.05).
CONCLUSIONS: Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2.
BACKGROUND: Shanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab.