The blood-brain barrier presents a major challenge for the delivery of therapeutic agents to the brain; however, it can be transiently opened by combining low intensity ultrasound with microbubble infusion. Studies evaluating this technology have largely been performed in rodents, including models of neurological conditions. However, despite promising outcomes in terms of drug delivery and the amelioration of neurological impairments, the potential for long-term adverse effects presents a major concern in the context of clinical applications.Methods: To fill this gap, we repeatedly treated 12-month-old wild-type mice with ultrasound, followed by a multimodal analysis for up to 18 months of age.Results: We found that spatial memory in these aged mice was not adversely affected as assessed in the active place avoidance test. Sholl analysis of Golgi impregnations in the dentate gyrus of the hippocampus did not reveal any changes to the neuronal cytoarchitecture. Long-term potentiation, a cellular correlate of memory, was still achievable, magnetic resonance spectroscopy revealed no major changes in metabolites, and diffusion tensor imaging revealed normal microstructure and tissue integrity in the hippocampus. More specifically, all measures of diffusion appeared to support a neuroprotective effect of ultrasound treatment on the brain.Conclusion: This multimodal analysis indicates that therapeutic ultrasound for blood-brain barrier opening is safe and potentially protective in the long-term, underscoring its validity as a potential treatment modality for diseases of the brain.

Purpose: Reduced bone strength is associated with a loss of bone mass, usually evaluated by dual-energy X-ray absorptiometry, although it is known that the bone microstructure also affects the bone strength. Here, a method is proposed to measure (in laboratory) the bone volume-to-total volume ratio by single-sided NMR scanners, which is related to the microstructure of the trabecular bone. Methods: Three single-sided scanners were used on animal bone samples. These low-field, mobile, low-cost devices are able to detect the NMR signal, regardless of the sample sizes, without the use of ionizing radiations, with the further advantage of signal localization offered by their intrinsic magnetic field gradients. Results: The performance of the different single-sided scanners have been discussed. The results have been compared with bone volume-to-total volume ratio by micro CT and MRI, obtaining consistent values.Conclusions: Our results demonstrate the feasibility of the method for laboratory analyses, which are useful for measurements like porosity on bone specimens. This can be considered as the first step to develop an NMR method based on the use of a mobile single-sided device, for the diagnosis of osteoporosis, through the acquisition of the signal from the appendicular skeleton, allowing for low-cost, wide screening campaigns. Magn Reson Med 79:501-510,

Background: The cerebellum and cerebral cortex form the most important cortico-cerebellar system in the brain. However, diffusion magnetic resonance imaging (MRI)-based tractography of the connecting white matter between the cerebellum and cerebral cortex, which support language function, has not been extensively reported on. This work aims to serve as a guideline for facilitating the analysis of white matter tracts along the language-related cerebro-cerebellar pathway (LRCCP), which includes the corticopontine, pontocerebellar, corticorubral, rubroolivary, olivocerebellar, and dentatorubrothalamic tracts. Methods:The LRCCP templates were developed via processing the high-resolution, population-averaged atlas available in the Human Connectome Project (HCP)-1065 dataset (2017 Q4, 1200-subject release) in DSI Studio. The deterministic tracking was performed with the manually selected regions of interest (ROIs) on this atlas according to prior anatomic knowledge. Templates were then applied to the MRI datasets of 30 health participants acquired from a single hospital to verify the practicability of the tracking. The diffusion tensor and shape analysis metrics were calculated for all LRCCP tracts. Differences in the tracking metrics between the left and right hemispheres were compared, and the related white matter asymmetry was discussed. Results:The LRCCP templates were successfully created and applied to healthy participants for quantitative analysis. Significantly higher mean fractional anisotropy (FA) values were discovered on the left (L) corticorubral tract [L, 0.43±0.02 vs. right (R), 0.41±0.02; P<0.01] and left dentatorubrothalamic tract (L, 0.47±0.02 vs. R, 0.46±0.02; P<0.01). Significant differences in tract volume and streamline number were observed between the corticopontine, corticorubral, and dentatorubrothalamic tracts. The size of the right corticopontine and corticorubral tracts were smaller, and both had smaller streamline numbers and innervation areas when compared with the contralateral sides. The R dentatorubrothalamic tract showed a

Brain arteriovenous malformation (AVM), a presumed congenital lesion, may involve traditional language areas but usually does not lead to language dysfunction unless it ruptures. The objective of this research was to study right-hemispheric language reorganization patterns in patients with brain AVMs using functional magnetic resonance imaging (fMRI). We prospectively enrolled 30 AVM patients with lesions involving language areas and 32 age-and sex-matched healthy controls. Each subject underwent fMRI during three language tasks: visual synonym judgment, oral word reading, and auditory sentence comprehension. The activation differences between the AVM and control groups were investigated by voxelwise analysis. Lateralization indices (LIs) for the frontal lobe, temporal lobe, and cerebellum were compared between the two groups, respectively. Results suggested that the language functions of AVM patients and controls were all normal. Voxelwise analysis showed no significantly different activations between the two groups in visual synonym judgment and oral word reading tasks. In auditory sentence comprehension task, AVM patients had significantly more activations in the right precentral gyrus (BA 6) and right cerebellar lobule VI (AAL 9042). According to the LI results, the frontal lobe in oral word reading task and the temporal lobe in auditory sentence comprehension task were significantly more right-lateralized in the AVM group. These findings suggest that for patients with AVMs involving language cortex, different language reorganization patterns may develop for different language functions. The recruitment of brain areas in the right cerebral and cerebellar hemispheres may play a compensatory role in the reorganized language network of AVM patients.

No abstract

Background and Purpose: Language dysfunction is rarely seen in patients with unruptured brain arteriovenous malformation (AVM) albeit the AVM nidus involving language areas, which provides a unique disease model to study language reorganization. The objective of this study was to investigate the impairment and reorganization patterns and characteristics of language-related white matter in AVMs located at different brain areas. Methods: Thirty-three patients with AVMs involving language areas were prospectively enrolled. Patients were categorized into 3 groups according to the lesion locations: the frontal (14 patients), temporal (15 patients), and parietal groups (4 patients). Thirty age- and sex-matched healthy controls were enrolled as comparison. All participants underwent diffusion tensor imaging scans, and automated fiber quantification method was applied to quantitatively study the difference of segmented language-related white matter connectivity between 3 AVM groups and control group. Results: Language functions were normal in all subjects according to Western Aphasia Battery test. In the frontal group, fractional anisotropy (FA) value decreased in the left arcuate fascicle and increased in left superior longitudinal fasciculus and uncinate fascicle; in the temporal group, FA values decreased in left inferior fronto-occipital fascicle and inferior longitudinal fascicle and increased in right anterior thalamic radiation and uncinate fascicle; in the parietal group, FA values decreased in left arcuate fascicle and inferior longitudinal fascicle and increased in bilateral anterior thalamic radiations and uncinate fascicles and right inferior fronto-occipital fascicle. In fascicles with decreased FA values, the increase of radial diffusivity was common, and fascicles with increased FA values usually presented along with increased axial diffusivity values. Conclusions: Remodeling of language-related white matter occurs when traditional language areas are involved by AVM nidus, and its reorganization patterns vary with locations of AVM nidus. Fascicle impairment is mainly caused by the myelin deficits, and its plasticity may be dominated by the axon remodeling procedure.

No abstract

Objectives Motivated by the similar appearance of malignant breast lesions in high b-value diffusion-weighted imaging (DWI) and positron emission tomography, the purpose of this work was to evaluate the applicability of a threshold isocontouring approach commonly used in positron emission tomography to analyze DWI data acquired from female human breasts with minimal interobserver variability. Methods Twenty-three female participants (59.4 ± 10.0 years) with 23 lesions initially classified as suggestive of cancers in x-ray mammography screening were subsequently imaged on a 1.5-T magnetic resonance imaging scanner. Diffusion-weighted imaging was performed prior to biopsy with b values of 0, 100, 750, and 1500 s/mm2. Isocontouring with different threshold levels was performed on the highest b-value image to determine the voxels used for subsequent evaluation of diffusion metrics. The coefficient of variation was computed by specifying 4 different regions of interest drawn around the lesion. Additionally, a receiver operating statistical analysis was performed. Results Using a relative threshold level greater than or equal to 0.85 almost completely suppresses the intra-individual and inter-individual variability. Among 4 studied diffusion metrics, the diffusion coefficients from the intravoxel incoherent motion model returned the highest area under curve value of 0.9. The optimal cut-off diffusivity was found to be 0.85 μm2/ms with a sensitivity of 87.5% and specificity of 90.9%. Conclusion Threshold isocontouring on high b-value maps is a viable approach to reliably evaluate DWI data of suspicious focal lesions in magnetic resonance mammography.