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DOI： 10.1161/STROKEAHA.123.044606

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DOI： 10.3174/ajnr.A8041

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DOI： 10.1186/s12987-023-00464-x

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DOI： 10.1016/j.mri.2023.04.006

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DOI： 10.3233/JAD-230068

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers in Aging Neuroscience  

The blood–brain barrier (BBB) plays important roles in the maintenance of brain homeostasis. Its main role includes three kinds of functions: (1) to protect the central nervous system from blood-borne toxins and pathogens; (2) to regulate the exchange of substances between the brain parenchyma and capillaries; and (3) to clear metabolic waste and other neurotoxic compounds from the central nervous system into meningeal lymphatics and systemic circulation. Physiologically, the BBB belongs to the glymphatic system and the intramural periarterial drainage pathway, both of which are involved in clearing interstitial solutes such as β-amyloid proteins. Thus, the BBB is believed to contribute to preventing the onset and progression for Alzheimer’s disease. Measurements of BBB function are essential toward a better understanding of Alzheimer’s pathophysiology to establish novel imaging biomarkers and open new avenues of interventions for Alzheimer’s disease and related dementias. The visualization techniques for capillary, cerebrospinal, and interstitial fluid dynamics around the neurovascular unit in living human brains have been enthusiastically developed. The purpose of this review is to summarize recent BBB imaging developments using advanced magnetic resonance imaging technologies in relation to Alzheimer’s disease and related dementias. First, we give an overview of the relationship between Alzheimer’s pathophysiology and BBB dysfunction. Second, we provide a brief description about the principles of non-contrast agent-based and contrast agent-based BBB imaging methodologies. Third, we summarize previous studies that have reported the findings of each BBB imaging method in individuals with the Alzheimer’s disease continuum. Fourth, we introduce a wide range of Alzheimer’s pathophysiology in relation to BBB imaging technologies to advance our understanding of the fluid dynamics around the BBB in both clinical and preclinical settings. Finally, we discuss the challenges of BBB imaging techniques and suggest future directions toward clinically useful imaging biomarkers for Alzheimer’s disease and related dementias.

DOI： 10.3389/fnagi.2023.1111448

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers in Neurology  

Background: R2* relaxometry and quantitative susceptibility mapping can be combined to distinguish between microstructural changes and iron deposition in white matter. Here, we aimed to explore microstructural changes in the white matter associated with clinical presentations such as cognitive impairment in patients with idiopathic normal-pressure hydrocephalus (iNPH) using R2* relaxometry analysis in combination with quantitative susceptibility mapping. Methods: We evaluated 16 patients clinically diagnosed with possible or probable iNPH and 18 matched healthy controls (HC) who were chosen based on similarity in age and sex. R2* and quantitative susceptibility mapping were compared using voxel-wise and atlas-based one-way analysis of covariance (ANCOVA). Finally, partial correlation analyses were performed to assess the relationship between R2* and clinical presentations. Results: R2* was lower in some white matter regions, including the bilateral superior longitudinal fascicle and sagittal stratum, in the iNPH group compared to the HC group. The voxel-based quantitative susceptibility mapping results did not differ between the groups. The atlas-based group comparisons yielded negative mean susceptibility values in almost all brain regions, indicating no clear paramagnetic iron deposition in the white matter of any subject. R2* and cognitive performance scores between the left superior longitudinal fasciculus (SLF) and right sagittal stratum (SS) were positively correlated. In addition to that, R2* and gait disturbance scores between left SS were negatively correlated. Conclusion: Our analysis highlights the microstructural changes without iron deposition in the SLF and SS, and their association with cognitive impairment and gait disturbance in patients with iNPH.

DOI： 10.3389/fneur.2023.1251230

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To develop and validate a novel noncontrast time-resolved magnetic resonance angiography (NC TR-MRA) using consecutive beam pulses with variable flip angles for visualizing hemodynamics in the pulmonary artery, we performed phantom and volunteer studies and applied the novel NC TR-MRA to a 51-year-old woman with pulmonary arteriovenous malformation (PAVM).The novel NC TR-MRA sequence utilized consecutive multiple-beam saturation pulses with variable flip angles considering venous blood T1 relaxation to alter the visualized blood signal length. The flowing blood signal length is suppressed according to the number of beam saturation pulses. NC TR-MRA in each flow phase was assessed by subtracting the images with and without beam saturation pulses. In the flow phantom study, three flow velocities were used to simulate physiological pulmonary arterial blood flow. Signal profiles along the flow direction were evaluated in each flow phase. In the volunteer study, five healthy volunteers were recruited, and NC TR-MRA was applied to evaluate relationships between the flow-saturated time and signal enhancement rates. Four regions of interest (ROIs) were determined on the proximal and distal portions of the right basal artery. A patient with PAVM was included to validate whether a PAVM lesion could be visualized using NC TR-MRA. The visualized flow signal lengths extended proportionally with the number of beam saturation pulses in the steady-flow phantom at all velocities. In the volunteer study, NC TR-MRA images showed signal enhancement from the proximal to distal portions of the right basal artery with increase in the flow-saturated time. Signal enhancement rates in all ROIs were significantly positively correlated with the flow-saturated time (p < 0.001 in all ROIs). Further, the lesion and its hemodynamics could be explicitly visualized in the patient with PAVM. Hence, NC TR-MRA using beam saturation pulse can visualize the hemodynamics of the pulmonary artery and may be useful for diagnosing and following patients with PAVM.

DOI： 10.1016/j.mri.2022.09.001

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMC Neurology  

Background: Mild cognitive impairment in Parkinson’s disease (PD-MCI) is associated with an increased risk of cognitive decline. PD-MCI is characterized by impairments in executive function and visuospatial recognition. The visuospatial n-back test is useful for assessing both domains. The 0-back test reflects visuospatial recognition, while the 1-back and 2-back tests reflect working memory. Cholinesterase inhibitors are effective in the treatment of PD-MCI and dementia in PD (PDD). Although some studies have reported the efficacy of memantine for PDD, the therapeutic efficacy of memantine in patients with PD-MCI remains uncertain. Methods: This study aimed to investigate the effects of memantine on brain function in patients with PD-MCI, using a randomized double-blinded crossover protocol and functional MRI (fMRI). Ten patients who completed 16 weeks of follow-up were included. They were randomly assigned to either the memantine or placebo. Patients in the memantine group received 5 mg/day of memantine in the first week. The memantine dose was increased by 5 mg/day per week, until a final dose of 20 mg/day. Patients in the placebo group received the placebo following the same regimen as memantine. After the intervention, they underwent a 4 weeks washout period. Following the crossover protocol, a second intervention was conducted after the washout period. In each intervention, fMRI and neuropsychological tests were performed at the maximum dose period. Comparing the memantine and placebo groups, we investigated difference in the brain regions using the visuospatial n-back test. Results: There were no significant regions enhanced by memantine comparing with placebo at any load of n-back tests. In contrast, exploring regions reduced by memantine, we found significant reduction of activations within right lingual gyrus and left superior frontal gyrus in comparison between 2-back and 0-back test. A number of correct answers of the 2-back test and time to complete Trail Making Test-A were worse during memantine intervention. Conclusions: Memantine did not improve visuospatial working memory of the patients with PD-MCI. Treatment for PD should be planned carefully considering the impact on cognitive function. Further study is needed to establish new therapeutic strategy. Trial registration: UMIN000046104. Retrospectively registered. First registration date: 28 Sept 2017.

DOI： 10.1186/s12883-022-02699-x

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: To examine the effect of apolipoprotein E (APOE) ɛ4 dose on blood-brain barrier (BBB) clearance function, evaluated using an advanced MRI technique and analyse its correlation with brain iron and β-amyloid accumulation in the early stages of the Alzheimer's continuum. METHODS: In this single-centre observational prospective cohort study, 24 APOE ɛ4 non-carriers, 22 heterozygotes and 20 homozygotes in the early stages of the Alzheimer's continuum were scanned with diffusion-prepared arterial spin labelling, which estimates the water exchange rate across the BBB (kw). Participants also underwent quantitative susceptibility mapping, [11C]Pittsburgh compound B-positron emission tomography and neuropsychological testing. Using an atlas-based approach, we compared the regional kw of the whole brain among the groups and analysed its correlation with the neuroradiological and neuropsychological findings. RESULTS: The BBB kw values in the neocortices differed significantly among the groups (APOE ɛ4 non-carriers>heterozygotes>homozygotes). These values correlated with brain iron levels (frontal lobe: r=-0.476, 95% CI=-0.644 to -0.264, p=0.011; medial temporal lobe: r=-0.455, 95% CI=-0.628 to -0.239, p=0.017), β-amyloid loads (frontal lobe: r=-0.504, 95% CI=-0.731 to -0.176, p=0.015; medial temporal lobe: r=-0.452, 95% CI=-0.699 to -0.110, p=0.036) and neuropsychological scores, after adjusting for age, sex and APOE ɛ4 dose. INTERPRETATION: Our results suggest that an increased APOE ɛ4 dose is associated with decreased effective brain-waste clearance, such as iron and β-amyloid, through the BBB.

DOI： 10.1136/jnnp-2021-328519

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To investigate the spatial accuracy of delineating prostatic calcifications by quantitative susceptibility mapping (QSM) in comparison with computed tomography (CT), we conducted phantom and human studies. Five differently-sized spherical hydroxyapatites mimicking prostatic calcification (pseudo-calcification) were arranged in the order of their sizes at the center of a plastic container filled with gelatin. This calcification phantom underwent magnetic resonance (MR) imaging, including the multiple spoiled gradient-echo sequences (SPGR) for the QSM and CT as a reference. The volume of each pseudo-calcification and center-to-center distance between the pseudo-calcifications delineated by QSM and CT were measured. In the human study, eight patients with prostate cancer who underwent radiation therapy and had some prostatic calcifications were included. The patients underwent CT and SPGR and modified DIXON sequence for MR-only simulation. The hybrid QSM processing combined with the complex signals in the SPGR and water and fat fraction maps estimated from the modified DIXON sequence were used to reconstruct the pelvic susceptibility map in humans. The threshold of CT numbers was set at 130 HU, while the QSM images were manually segmented in the calcification phantom and human studies. In the phantom study, there was an excellent agreement in the pseudo-calcification volumes between QSM and CT (y = 1.02x - 7.38, R2  = 0.99). The signal profiles had similar trends in CT and QSM. The center-to-center distances between the pseudo-calcifications in the phantom were also identical in QSM and CT. The calcification volumes were almost identical between the QSM and CT in the human study (y = 0.95x - 9.32, R2  = 1.00). QSM can offer geometric and volumetric accuracies to delineate prostatic calcifications, similar to CT. The prostatic calcification delineated by QSM may facilitate image-guided radiotherapy in the MR-only simulation workflow.

DOI： 10.1002/acm2.13469

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.parkreldis.2021.12.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

<sec><title>Background</title>The oxygen extraction fraction (OEF) has been applied to identify ischemic penumbral tissue, but is difficult to use in an urgent care setting. This study aimed to investigate whether an OEF map generated via magnetic resonance quantitative susceptibility mapping (QSM) could help identify the ischemic penumbra in patients with acute ischemic stroke.

</sec><sec><title>Materials and Methods</title>This prospective imaging study included 21 patients with large anterior circulation vessel occlusion who were admitted &amp;lt;24 h after stroke onset and 21 age-matched healthy controls. We identified the ischemic penumbra as the region with a Tmax of &amp;gt;6 s during dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) and calculated the perfusion-core mismatch ratio between the ischemic penumbra and infarct core volumes. The OEF values were measured based on magnetic susceptibility differences between the venous structures and brain tissues using rapid QSM acquisition. Volumes with increased OEF values were compared to the ischemic penumbra volumes using an anatomical template.

</sec><sec><title>Results</title>Eleven patients had a perfusion-core mismatch ratio of ≥1.8, and reperfusion therapy was recommended. In these patients, the volumes with increased OEF values of &amp;gt;51.5%, which was defined using the anterior circulation territory OEF values from the 21 healthy controls, were positively correlated with the ischemic penumbra volumes (<italic>r</italic> = 0.636, 95% CI: 0.059 to 0.895, <italic>P</italic> = 0.035) and inversely correlated with the 30-day change in the National Institutes of Health Stroke Scale scores (<italic>r</italic> = −0.624, 95% CI: −0.891 to −0.039, <italic>P</italic> = 0.041).

</sec><sec><title>Conclusion</title>Tissue volumes with increased OEF values could predict ischemic penumbra volumes based on DSC-MRI, highlighting the potential of the QSM-derived OEF map as a penumbra biomarker to guide treatment selection in patients with acute ischemic stroke.

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DOI： 10.3389/fneur.2022.752450

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BACKGROUND: R2* relaxometry analysis combined with quantitative susceptibility mapping (QSM), which has high sensitivity to iron deposition, can distinguish microstructural changes of the white matter (WM) and iron deposition, thereby providing a sensitive and biologically specific measure of the WM owing to the changes in myelin and its surrounding environment. This study aimed to explore the microstructural WM alterations associated with cognitive impairment in patients with Parkinson's disease (PD) using R2* relaxometry analysis combined with QSM. MATERIALS AND METHODS: We enrolled 24 patients with PD and mild cognitive impairment (PD-MCI), 22 patients with PD and normal cognition (PD-CN), and 19 age- and sex-matched healthy controls (HC). All participants underwent Montreal Cognitive Assessment (MoCA) and brain magnetic resonance imaging, including structural three-dimensional T1-weighted images and multiple spoiled gradient echo sequence (mGRE). The R2* and susceptibility maps were estimated from the multiple magnitude images of mGRE. The susceptibility maps were used for verifying iron deposition in the WM. The voxel-based R2* of the entire WM and its correlation with cognitive performance were analyzed. RESULTS: In the voxel-based group comparisons, the R2* in the PD-MCI group was lower in some WM regions, including the corpus callosum, than R2* in the PD-CN and HC groups. The mean susceptibility values in almost all brain regions were negative and close-to-zero values, indicating no detectable paramagnetic iron deposition in the WM of all subjects. There was a significant positive correlation between R2* and MoCA in some regions of the WM, mainly the corpus callosum and left hemisphere. CONCLUSION: R2* relaxometry analysis for WM microstructural changes provided further biologic insights on demyelination and changes in the surrounding environment, supported by the QSM results demonstrating no iron existence. This analysis highlighted the potential for the early evaluation of cognitive decline in patients with PD.

DOI： 10.1016/j.nicl.2022.102938

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Alzheimer’s disease (AD) is the most common type of dementia and a distressing diagnosis for individuals and caregivers. Researchers and clinical trials have mainly focused on β-amyloid plaques, which are hypothesized to be one of the most important factors for neurodegeneration in AD. Meanwhile, recent clinicopathological and radiological studies have shown closer associations of tau pathology rather than β-amyloid pathology with the onset and progression of Alzheimer’s symptoms. Toward a biological definition of biomarker-based research framework for AD, the 2018 National Institute on Aging–Alzheimer’s Association working group has updated the ATN classification system for stratifying disease status in accordance with relevant pathological biomarker profiles, such as cerebral β-amyloid deposition, hyperphosphorylated tau, and neurodegeneration. In addition, altered iron metabolism has been considered to interact with abnormal proteins related to AD pathology thorough generating oxidative stress, as some prior histochemical and histopathological studies supported this iron-mediated pathomechanism. Quantitative susceptibility mapping (QSM) has recently become more popular as a non-invasive magnetic resonance technique to quantify local tissue susceptibility with high spatial resolution, which is sensitive to the presence of iron. The association of cerebral susceptibility values with other pathological biomarkers for AD has been investigated using various QSM techniques; however, direct evidence of these associations remains elusive. In this review, we first briefly describe the principles of QSM. Second, we focus on a large variety of QSM applications, ranging from common applications, such as cerebral iron deposition, to more recent applications, such as the assessment of impaired myelination, quantification of venous oxygen saturation, and measurement of blood– brain barrier function in clinical settings for AD. Third, we mention the relationships among QSM, established biomarkers, and cognitive performance in AD. Finally, we discuss the role of QSM as an imaging biomarker as well as the expectations and limitations of clinically useful diagnostic and therapeutic implications for AD.

DOI： 10.3389/fnins.2022.938092

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers in Human Neuroscience  

Aphasia is a language disorder that occurs after a stroke and impairs listening, speaking, reading, writing, and calculation skills. Patients with post-stroke aphasia in Japan are increasing due to population aging and the advancement of medical treatment. Opportunities for adequate speech therapy in chronic stroke are limited due to time constraints. Recent studies have reported that intensive speech therapy for a short period of time or continuous speech therapy using high-tech equipment, including speech applications (apps, can improve aphasia even in the chronic stage. However, its underlying mechanism for improving language function and its effect on other cognitive functions remains unclear. In the present study, we investigated whether intensive speech therapy using a newly developed speech support app could improve aphasia and other cognitive functions in patients with chronic stroke. Furthermore, we examined whether it can alter the brain network related to language and other cortical areas. Thus, we conducted a prospective, single-comparison study to examine the effects of a new speech support app on language and cognitive functions and used resting state functional MRI (rs-fMRI) regions of interest (ROI) to ROI analysis to determine changes in the related brain network. Two patients with chronic stroke participated in this study. They used the independent speech therapy system to perform eight sets of 20 randomly presented words/time (taking approximately 20 min), for 8 consecutive weeks. Their language, higher cognitive functions including attention function, and rs-fMRI, were evaluated before and after the rehabilitation intervention using the speech support app. Both patients had improved pronunciation, daily conversational situations, and attention. The rs-fMRI analysis showed increased functional connectivity of brain regions associated with language and attention related areas. Our results show that intensive speech therapy using this speech support app can improve language and attention functions even in the chronic stage of stroke, and may be a useful tool for patients with aphasia. In the future, we will conduct longitudinal studies with larger numbers of patients, which we hope will continue the trends seen in the current study, and provide even stronger evidence for the usefulness of this new speech support app.

DOI： 10.3389/fnhum.2022.870733

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PLoS ONE  

Purpose The purpose of this study was to evaluate the usefulness of turbo spin-echo (TSE) DWI with fusion images in the T-staging compared with T2-weighted imaging (T2WI) alone and conventional echo-planner imaging (EPI) DWI. Methods In this prospective study, 4-mm-thick axial EPI-DWI, TSE-DWI, and T2WI were performed with the same slice locations for 20 patients with rectal cancer. Fusion images of DWI and T2WI were created for both EPI-DWI and TSE-DWI. Ten readers independently diagnosed the T-stages and scored the degree of confidence referring to T2WI alone and then to DWI, T2WI, and fusion images (DWI+T2WI) for each EPI-DWI and TSE-DWI. Visual score assessments of image quality were performed for each DWI. Results Inter-observer agreement of T-staging for 10 readers was slight on T2WI alone but fair on EPI-DWI+T2WI and excellent on TSE-DWI+T2WI images. No readers gave higher confidence scores for T2WI compared to EPI/TSE-DWI+T2WI and for EPI-DWI+T2WI compared to TSE-DWI+T2WI. In seven pathologically-proven cases, poor, poor to slight, and fair to perfect agreements with the pathological T-stage were observed with T2WI alone, EPI-DWI +T2WI, and TSE-DWI+T2WI, respectively. All readers gave higher scores regarding image distortion and lower scores regarding image noise for TSE-DWI compared to EPI-DWI. For DWI utility, higher scores were assigned for TSE-DWI compared to EPI-DWI in 7 readers and there were no significant differences in the other 3 readers. Conclusion TSE-DWI images might be more appropriate for image fusion with T2WI and rectal cancer T-staging compared with EPI-DWI and T2WI alone.

DOI： 10.1371/journal.pone.0249433

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.3174/AJNR.A6473

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BACKGROUND: The causative mechanisms of idiopathic normal-pressure hydrocephalus (iNPH) symptoms are currently unknown. PURPOSE: To assess the dynamic changes in the apparent diffusion coefficient (ADC) during the cardiac cycle (ΔADC) of the brain before and after the lumbar tap and shunt surgery for the purpose of determining changes in hydrodynamic and biomechanical properties in the brain after cerebrospinal fluid (CSF) drainage for iNPH. STUDY TYPE: Retrospective. SUBJECTS: Overall, 22 patients suspected to have iNPH were examined before and after the lumbar tap and were divided into patients who showed symptomatic improvements (positive group, n = 17) and those without improvement (negative group, n = 5) after the lumbar tap. Seven patients in the positive group were examined after the shunt surgery. FIELD STRENGTH/SEQUENCE: 1.5T, electrocardiographically synchronized single-shot diffusion echo-planar imaging. ASSESSMENT: The frontal white matter ΔADC and mean ADC (ADCmean ) were compared between before and 24 hours after lumbar tap and from 1 week to 1 month after the shunt surgery. STATISTICAL TESTS: Wilcoxon signed-rank test was used. P < 0.05 was considered statistically significant. RESULTS: The ΔADC after the lumbar tap in the positive group was significantly lower than that before (P < 0.05), whereas no significant difference was found in the negative group (P = 0.23). After the lumbar tap, ΔADC decreased in 16 of 17 patients in the positive group, whereas ADCmean did not significantly change (P = 0.96). After the shunt surgery, ΔADC decreased in all seven patients (P < 0.05), whereas ADCmean did not significantly change (P = 0.87). DATA CONCLUSION: The frontal white matter ΔADC in iNPH decreased after the lumbar tap and shunt surgery. ΔADC analysis may provide detailed information regarding changes in the hydrodynamic and biomechanical properties through CSF drainage. LEVEL OF EVIDENCE: 4. TECHNICAL EFFICACY STAGE: 4.

DOI： 10.1002/jmri.27412

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Magnetic Resonance in Medicine  

We prospectively evaluated thin-slice coronal turbo spin-echo (TSE) diffusion-weighted imaging (DWI) covering a larger area with the recently-developed techniques on a 3T MRI scanner, compared with echo-planar imaging (EPI)-DWI in patients undergoing routine hand MRI. Visual score assessment and apparent diffusion coefficient (ADC) measurement were performed for patients with suspected hand tumors. TSE-DWI was superior to EPI-DWI, with less image distortion. The visual score and ADC comparison assessments proved that the image noise of TSE-DWI was acceptable.

DOI： 10.2463/mrms.tn-2019-0115

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To clarify the temperature dependence of susceptibility estimated by quantitative susceptibility mapping (QSM) analysis, we investigated the relationship between temperature and susceptibility using a cylinder phantom with varying temperatures. Six solutions with various concentrations of superparamagnetic iron oxide (SPIO) nanoparticles were employed. These tubes were placed in a cylinder phantom and surrounded with water. The temperature of the circulated water was adjusted to change the temperature in the cylinder phantom from 25.8 °C to 42.5 °C. The cylinder phantom was scanned via a three-dimensional multiple spoiled gradient-echo sequence for R2* and QSM analyses with varying temperatures. The relationships between temperature, susceptibility, and R2* values were determined. Moreover, the temperature coefficients of susceptibility (χ-Tc) and (R2*-Tc) were calculated at each concentration and the linearities in these indices against each SPIO concentration were validated. Significant inverse correlations were found between temperature, susceptibility, and R2* values at each SPIO concentration due to the decrease in paramagnetic iron susceptibility that occurred with increasing temperature based on Curie's law. Moreover, although there were significant correlations between the susceptibility and R2* values at any temperature, the slopes of the regression lines grew in height with greater temperatures. The percentage of difference per Celsius degree in susceptibility in any SPIO concentration was lower than the corresponding finding among the R2* results. There were strong linearities between the SPIO concentration, χ-Tc (r = -0.994; p < 0.001), and R2*-Tc (r = -0.998; p < 0.001). The χ-Tc and R2*-Tc outcomes in a particular voxel varied considerably with the iron contents. Although there was an inverse correlation noted between temperature and susceptibility, the susceptibility analysis showed smaller temperature dependence relative to the R2* analysis. QSM analysis might be a more suitable option for magnetic resonance-based iron quantification in comparison with R2* relaxometry.

DOI： 10.1016/j.mri.2020.08.012

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OBJECTIVE: To assess the relationship among iron accumulation, blood-brain barrier (BBB) damage, and cognitive function in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: We enrolled 21 patients with NOTCH3 mutations and 21 age-matched healthy controls in this cross-sectional study. All participants underwent global physical and cognitive assessments and brain MRI using voxel-based quantitative susceptibility mapping (QSM; iron deposition measure) and dynamic contrast-enhanced MRI (BBB permeability measure). We compared behavioral and imaging data between the groups and analyzed the correlations in each group. RESULTS: Among 21 NOTCH3 mutation carriers, 10 were symptomatic and 11 asymptomatic. Montreal Cognitive Assessment scores were significantly different among the groups (symptomatic < asymptomatic < control participants). Voxel-based QSM analysis revealed that the symptomatic group had higher QSM values than did the asymptomatic group in the putamen, caudate nucleus, temporal pole, and centrum semiovale. These QSM values were positively correlated with regional BBB permeabilities (putamen: r = 0.57, p = 0.006; caudate nucleus: r = 0.51, p = 0.019; temporal pole: r = 0.48, p = 0.030; centrum semiovale: r = 0.45, p = 0.044) and negatively correlated with Montreal Cognitive Assessment scores (caudate nucleus: r = -0.53, p = 0.012; temporal pole: r = -0.56, p = 0.008). CONCLUSIONS: This study showed that cerebral iron burden was associated with regional BBB permeability and cognitive dysfunction in patients with CADASIL, highlighting the potential of these imaging techniques as auxiliary biomarkers to monitor the course of small vessel disease.

DOI： 10.1212/WNL.0000000000010148

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OBJECTIVE: The objective of this study was to assess the relationship between nigrostriatal magnetic susceptibility and dopamine transporter abnormality and their associations with behavioral and cognitive impairments in patients with Parkinson's disease (PD). METHODS: For this case-control study, we enrolled 41 patients with PD and 20 age-matched healthy controls. All participants underwent global physical and cognitive assessments, 3-Tesla brain magnetic resonance imaging including quantitative susceptibility mapping (QSM; iron deposition measure), and 123 I-N-v-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane single-photon emission computed tomography (dopamine transporter measure). We subdivided the striatum into the putamen, caudate nucleus, and nucleus accumbens and measured the nigrostriatal QSM values and dopamine transporter-specific binding ratios using an atlas-based approach. RESULTS: The patients with PD had higher QSM values in the substantia nigra and subdivisions of the striatum than did the healthy controls. The striatal dopamine transporter-specific binding ratios were not correlated with the QSM values of the substantia nigra but were inversely correlated with those of the striatum (putamen, r = -0.478, P = 0.009; caudate nucleus, r = -0.462, P = 0.011). The QSM values of the putamen were positively correlated with motor parkinsonism scores (Movement Disorder Society Unified Parkinson's Disease Rating Scale, r = 0.505, P = 0.003), and those of the caudate nucleus were negatively correlated with cognitive impairment scores (Montreal Cognitive Assessment, r = -0.525, P < 0.001). CONCLUSIONS: This study showed that striatal iron accumulations were correlated with dopaminergic deficits and neurophysiological signs in patients with PD, highlighting the potential of QSM as an auxiliary biomarker for parkinsonism and cognitive dysfunction. © 2020 International Parkinson and Movement Disorder Society.

DOI： 10.1002/mds.28077

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

This study aimed to develop and test a simultaneous acquisition and analysis pipeline for voxel-based magnetic susceptibility and morphometry (VBMSM) on a single dataset using young volunteers, elderly healthy volunteers, and an Alzheimer's disease (AD) group. 3D T-1-weighted and multi-echo phase images for VBM and quantitative susceptibility mapping (QSM) were simultaneously acquired using a magnetization-prepared spoiled turbo multiple gradient echo sequence with inversion pulse for QSM (MP-QSM). The magnitude image was split into gray matter (GM) and white matter (WM) and was spatially normalized. The susceptibility map was reconstructed from the phase images. The segmented image and susceptibility map were compared with those obtained from conventional multiple spoiled gradient echo (mGRE) and MP-spoiled gradient echo (MP-GRE) in healthy volunteers to validate the availability of MP-QSM by numerical measurements. To assess the feasibility of the VBMSM analysis pipeline, voxel-based comparisons of susceptibility and morphometry in MP-QSM were conducted in volunteers with a bimodal age distribution, and in elderly volunteers and the AD group, using spatially normalized GM and WM volume images and a susceptibility map. GM/WM contrasts in MP-QSM, MP-GRE, and mGRE were 0.14 +/- 0.011, 0.17 +/- 0.015, and 0.045 +/- 0.010, respectively. Segmented GM and WM volumes in the MP-QSM closely coincided with those in the MP-GRE. Region of interest analyses indicated that the mean susceptibility values in MP-QSM were completely in agreement with those in mGRE. In an evaluation of the aging effect, a significant increase and decrease in susceptibility and volume were found by VBMSM in deep GM and WM, respectively. Between the elderly volunteers and the AD group, the characteristic susceptibility and volume changes in GM and WM were observed. The proposed MP-QSM sequence makes it possible to acquire acceptable-quality images for simultaneous analysis and determine brain atrophy and susceptibility distribution without image registration by using voxel-based analyses.

DOI： 10.1002/nbm.4272

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Language：Japanese   Publishing type：Research paper (scientific journal)  

© 2020 American Society of Neuroradiology. All rights reserved. BACKGROUND AND PURPOSE: Parkinson disease is related to neurodegeneration and iron deposition in the substantia nigra pars compacta and nigrosome 1. However, visualization of nigrosome 1 via MR imaging is poor owing to the bilateral asymmetry, regardless of whether it is healthy. We focused on the magic angle and susceptibility effect and evaluated the anatomic slant structure of nigrosome 1 by tilting subjects’ heads in the B0 direction. MATERIALS AND METHODS: To investigate the effectiveness of the magic angle, we tilted the volunteers’ heads to the right and left in the B0 direction or not at all for evaluating correlations between the degree of head tilting and visualization of the right nigrosome 1 and left nigrosome 1 using 3D spoiled gradient-echo sequences with multiecho acquisitions. We evaluated the susceptibility of nigrosome 1 and the local field using quantitative susceptibility mapping to assess static magnetic field inhomogeneity. RESULTS: The heads tilted to the right and left showed significantly higher contrasts of nigrosome 1 and the substantia nigra pars compacta than the nontilted heads. No significant differences were observed in the visualization and susceptibility between the right nigrosome 1 and left nigrosome 1 for each head tilt. The effect of the magic angle was remarkable in the nontilted heads. This finding was supported by quantitative susceptibility mapping because the anatomic slant structure of nigrosome 1 was coherent between the axis of nigrosome 1 and the magic angle. CONCLUSIONS: The asymmetric visualization of nigrosome 1 is affected by the magic angle and susceptibility. The anatomic slant structure of nigrosome 1 causes these challenges in visualization.

DOI： 10.3174/ajnr.A6338

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Magnetic Resonance in Medicine  

To mitigate the susceptibility inhomogeneity induced by radio-frequency transmit phase error through the whole brain in quantitative susceptibility mapping (QSM) using single-echo gradient echo sequence, we developed a novel single-step QSM reconstruction algorithm and compared it with a previous algorithm in five healthy volunteers. The proposed algorithm had effectively suppressed the susceptibility inhomogeneity through the whole brain and achieved acceptable quality, similar to that of the susceptibility map calculated from a multi-echo gradient echo sequence.

DOI： 10.2463/mrms.tn.2018-0066

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CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Brain iron accumulation has been proposed as one of the pathomechanisms in Parkinson's disease (PD). This study aimed to examine the whole-brain pattern of iron accumulation associated with cognitive impairment in patients with PD using voxel-based quantitative susceptibility mapping analysis. METHODS: We enrolled 24 patients with PD and mild cognitive impairment, 22 patients with PD and normal cognition, and 20 age-matched healthy controls in this cross-sectional study. All participants underwent global cognitive and physical assessments and brain MRI. Using a combined method of voxel-based morphometry and quantitative susceptibility mapping, we compared the voxel-wise magnetic susceptibility of the whole brain between the groups and analyzed its correlation with the cognitive and behavioral data. RESULTS: The PD and mild cognitive impairment group had lower Montreal Cognitive Assessment (MoCA) score than the PD and normal cognition and healthy control groups. There were no gray matter volumetric differences between the groups. In contrast, the voxel-based quantitative susceptibility mapping analysis showed that the PD and mild cognitive impairment group had significantly higher quantitative susceptibility mapping values in the cuneus, precuneus, caudate head, fusiform gyrus, and orbitofrontal cortex than did the PD and normal cognition group. These quantitative susceptibility mapping values were negatively correlated with the MoCA scores in the PD patients (cuneus: r = -0.510, P < .001; caudate head: r = -0.458, P = 0.002). CONCLUSIONS: This study suggests that cognitive impairment in PD is associated with cerebral iron burden and highlights the potential of quantitative susceptibility mapping as an auxiliary biomarker for early evaluation of cognitive decline in patients with PD. © 2019 International Parkinson and Movement Disorder Society.

DOI： 10.1002/mds.27717

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1088/1361-6560/ab02cc

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The purpose of this study was to evaluate differences in parameters of diffusion kurtosis imaging (DKI) and minimum apparent diffusion coefficient (ADCmin) between benign and malignant musculoskeletal tumors. MATERIALS AND METHODS: In this prospective study, 43 patients were scanned using a DKI protocol on a 3-T MR scanner. Eligibility criteria were: non-fatty, non-cystic soft tissue or osteolytic tumors; > 2 cm; location in the retroperitoneum, pelvis, leg, or neck; and no prior treatment. They were clinically or histologically diagnosed as benign (n = 27) or malignant (n = 16). In the DKI protocol, diffusion-weighted imaging was performed using four b values (0-2000 s/mm2) and 21 diffusion directions. Mean kurtosis (MK) values were calculated on the MR console. A recently developed software application enabling reliable calculation was used for DKI analysis. RESULTS: MK showed a strong correction with ADCmin (Spearman's rs = 0.95). Both MK and ADCmin values differed between benign and malignant tumors (p < 0.01). For benign and malignant tumors, the mean MK values (± SD) were 0.49 ± 0.17 and 1.14 ± 0.30, respectively, and ADCmin values were 1.54 ± 0.47 and 0.49 ± 0.17 × 10-3 mm2/s, respectively. At cutoffs of MK = 0.81 and ADCmin = 0.77 × 10-3 mm2/s, the specificity and sensitivity for diagnosis of malignant tumors were 96.3 and 93.8% for MK and 96.3 and 93.8% for ADCmin, respectively. The areas under the curve were 0.97 and 0.99 for MK and ADCmin, respectively (p = 0.31). CONCLUSIONS: MK and ADCmin showed high diagnostic accuracy and strong correlation, reflecting the accuracy of MK. However, no clear added value of DKI could be demonstrated in differentiating musculoskeletal tumors.

DOI： 10.1007/s00256-018-2946-0

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Language：English   Publishing type：Research paper (scientific journal)  

Rapid eye movement sleep behavior disorder is parasomnia characterized by symptoms of dream enactment and loss of muscle atonia during rapid eye movement sleep. Mild motor impairment is present in some patients with rapid eye movement sleep behavior disorder and presumed to be a risk factor for conversion to synucleinopathies. The purpose of this study is to identify patients with mild motor impairment by evaluating finger tapping and to investigate its pathophysiology. Twenty-three patients with rapid eye movement sleep behavior disorder and 20 healthy control subjects were recruited in the present study. We accurately evaluated finger tapping including amplitude, peak open, and close speed with a magnetic sensing device and identified patients with mild motor impairment. Moreover, we performed 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane SPECT and resting state functional MRI. 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane uptake for each bilateral caudate, anterior putamen, and posterior putamen was calculated and the resting state functional connectivity of sensorimotor network was analyzed. Using finger tapping parameters, we identified eight patients with mild motor impairment. In patients with mild motor impairment, all finger tapping parameters were significantly impaired when compared to patients with normal motor function, while they exhibited no significant differences in Unified Parkinson's Disease Rating Scale part III score. 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane uptake in the right posterior putamen, bilateral anterior putamen, and caudate was significantly lower when compared to healthy controls or patients with rapid eye movement sleep behavior disorder with normal motor function. These patients also exhibited decreased cortico-striatal functional connectivity and increased cortico-cerebellar functional connectivity when compared to healthy controls or patients with normal motor function. Our results show that mild motor impairment in rapid eye movement sleep behavior disorder evaluated by finger tapping task presented mild nigrostriatal dopaminergic dysfunction as well as alterations in resting state sensorimotor network. Although longitudinal follow up is necessary, such patients may have higher risk of short-term conversion to synucleinopathies.

DOI： 10.3389/fneur.2019.00802

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Publishing type：Research paper (scientific journal)   Publisher：Magnetic Resonance Imaging  

DOI： 10.1016/j.mri.2018.06.006

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Publishing type：Research paper (scientific journal)   Publisher：Magnetic Resonance Imaging  

DOI： 10.1016/j.mri.2018.03.013

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Publishing type：Research paper (scientific journal)   Publisher：Radiological Physics and Technology  

DOI： 10.1007/s12194-018-0460-7

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Publishing type：Research paper (scientific journal)   Publisher：British Journal of Radiology  

DOI： 10.1259/bjr.20170652

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Publishing type：Research paper (scientific journal)   Publisher：Polish Journal of Radiology  

DOI： 10.5114/pjr.2018.75622

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.14389/jsad.10.1_29

Publishing type：Research paper (scientific journal)   Publisher：Magnetic Resonance Imaging  

DOI： 10.1016/j.mri.2017.05.002

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Publishing type：Research paper (scientific journal)   Publisher：Magnetic Resonance Imaging  

DOI： 10.1016/j.mri.2017.02.006

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Publishing type：Research paper (scientific journal)   Publisher：Magnetic Resonance Imaging  

DOI： 10.1016/j.mri.2016.04.019

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Publishing type：Research paper (scientific journal)   Publisher：Frontiers in Psychiatry  

DOI： 10.3389/fpsyt.2016.00003

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.11318/mii.33.vii

Publishing type：Research paper (scientific journal)   Publisher：Abdominal Imaging  

DOI： 10.1007/s00261-015-0491-z

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Publishing type：Research paper (scientific journal)   Publisher：Computerized Medical Imaging and Graphics  

DOI： 10.1016/j.compmedimag.2014.12.004

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Publishing type：Research paper (scientific journal)   Publisher：Magnetic Resonance Imaging  

DOI： 10.1016/j.mri.2014.08.026

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Publishing type：Research paper (scientific journal)   Publisher：Journal of Vascular and Interventional Radiology  

DOI： 10.1016/j.jvir.2014.06.003

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Publishing type：Research paper (scientific journal)   Publisher：Radiological Physics and Technology  

DOI： 10.1007/s12194-013-0254-x

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Publishing type：Research paper (scientific journal)   Publisher：Acta Neurochirurgica, Supplementum  

DOI： 10.1007/978-3-7091-0956-4_38

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.11318/mii.29.23

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.11318/mii.29.20

Publishing type：Research paper (scientific journal)   Publisher：Radiology  

DOI： 10.1148/radiol.11101860

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PubMed

Publishing type：Research paper (scientific journal)  

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Fast spin echo(FSE)sequence has been widely recognized that the contrast of T₂ weighted image was affected by multi-refocusing pulses. The contrasts have never been investigated in case of echo space(ES)below 20msec although magnetic resonance imaging(MRI)developed such that the ES of multi-refocusing pulses could set at 5msec. To evaluate the contrasts of fat with short ES, we determined the signal intensities of the brain tissues and bottle phantom which consists of lard, water and bean oil. The signal intensities of all regions increased with decreasing echo spaces, due to the decoupling of J-coupling, excepting water signal intensity. In addition, the contrasts between the white matter and each region decreased with decreasing ES until 10ms and, however, did not change with decreasing ES over 10ms. The contrast between white and gray matter is also discussed. It is concluded that the contrast does not change in case of the echo space below 10ms.

DOI： 10.11318/mii.28.79

Language：English   Publishing type：Research paper (scientific journal)  

We evaluated regional apparent diffusion coefficient (ADC) change of the brain during the cardiac cycle (&Delta;ADC) . On a 1.5-T MRI, ECG-triggered single-shot diffusion echo planar imaging was used with sensitivity encoding, half scan and rectangular FOV techniques to minimize the bulk motion such as brain pulsation, i.e., data-sampling window of 3ms. &Delta;ADC image was calculated from maximum minus minimum ADC value of all cardiac phase images on a pixel-by-pixel basis. We determined &Delta;ADC in regions of parietal, frontal, temporal and occipital white matters (WM) in twelve healthy volunteers. Moreover, we assessed influences of scan parameters on &Delta;ADC. &Delta;ADC was affected by b-values, but unaffected by voxel size. There was no significant correlation between &Delta;ADC and ADC. The &Delta;ADC values in parietal WM at centrum semiovale level were significantly higher than those in temporal WM at basal ganglia level, although there was no significant difference in ADC values between among WM regions. &Delta;ADC analysis using appropriate scan parameter makes it possible to noninvasively obtain new and more detailed information on the regional brain condition.

DOI： 10.11318/mii.26.17

Language：English  

DOI： 10.1016/j.mri.2018.06.006

PubMed

Language：English  

DOI： 10.1016/j.mri.2018.03.013

PubMed

Language：English  

DOI： 10.1007/s12194-018-0460-7

PubMed

Language：English  

DOI： 10.1259/bjr.20170652

PubMed

Language：English  

DOI： 10.5114/pjr.2018.75622

PubMed

Language：English  

DOI： 10.1016/j.mri.2017.05.002

PubMed

Language：English  

DOI： 10.1016/j.mri.2017.02.006

PubMed

Language：English  

DOI： 10.1016/j.mri.2016.04.019

PubMed

Language：English  

DOI： 10.3389/fpsyt.2016.00003

PubMed

Language：English  

DOI： 10.1007/s00261-015-0491-z

PubMed

Language：English  

DOI： 10.1016/j.compmedimag.2014.12.004

PubMed

Language：English  

DOI： 10.1016/j.mri.2014.08.026

PubMed

Language：English  

DOI： 10.1016/j.jvir.2014.06.003

PubMed

Language：English  

DOI： 10.1007/s12194-013-0254-x

PubMed

Language：English  

DOI： 10.1148/radiol.11101860

PubMed

Language：Japanese  

PubMed

Language：Japanese  

PubMed

Event date： 2020

Language：English   Presentation type：Poster presentation  

Event date： 2019

Language：English   Presentation type：Poster presentation  

Event date： 2018

Language：English   Presentation type：Poster presentation  

Event date： 2017