Longitudinal Changes in Iron and Myelination Within Ischemic Lesions Associate With Neurological Outcomes: A Pilot Study.

BACKGROUND: Combined quantitative susceptibility mapping and R2* relaxometry can distinguish iron and myelin components in ischemic lesions. We aimed to investigate whether longitudinal changes in magnetic susceptibility and R2* values within ischemic lesions were associated with neurological outcomes. METHODS: In this single-center prospective study, we included patients, 20 to 90 years of age, who were consecutively admitted to the stroke care unit between August 2020 and March 2022 due to acute ischemic stroke. The participants underwent 2 instances of quantitative susceptibility mapping and R2* relaxometry scanning before and after stroke rehabilitation. We compared the changes in these quantitative measures across different subtypes of acute ischemic stroke. Multiple linear regression models were used to investigate the associations between the National Institutes of Health Stroke Scale scores and the mean magnetic susceptibility and R2* values in ischemic lesions. RESULTS: Among a total of 112 patients with acute ischemic stroke, 32 participants (aged 73.3±9.4 years; 20 men and 12 women) were evaluated. The median time from stroke onset to the first imaging was 5 days and that to the second imaging was 102 days. The changes in magnetic susceptibility values of branch atheromatous disease were higher than those of cardioembolism (mean difference, 0.018 [95% CI, 0.009-0.027] ppm; P<0.001) and lacunar (mean difference, 0.013 [95% CI, 0.005-0.020] ppm; P=0.004). Across all patients, the changes in National Institutes of Health Stroke Scale scores were associated with those of magnetic susceptibility values (coefficient, 0.311 [95% CI, 0.098-0.520]; P=0.017) but not with R2* values (coefficient, 0.114 [95% CI, -0.127 to 0.345]; P=0.291). CONCLUSIONS: The longitudinal changes in the magnetic susceptibility values within ischemic lesions were associated with neurological outcomes during the restorative stages poststroke in patients experiencing acute ischemic stroke. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000050719.

Quantitative susceptibility mapping for susceptibility source separation with adaptive relaxometric constant estimation (QSM-ARCS) from solely gradient-echo data.

To separate the contributions of paramagnetic and diamagnetic sources within a voxel, a magnetic susceptibility source separation method based solely on gradient-echo data has been developed. To measure the opposing susceptibility sources more accurately, we propose a novel single-orientation quantitative susceptibility mapping method with adaptive relaxometric constant estimation (QSM-ARCS) for susceptibility source separation. Moreover, opposing susceptibilities and their anisotropic effects were determined in healthy volunteers in the white matter. Multiple spoiled gradient echo and diffusion tensor imaging of ten healthy volunteers was obtained using a 3 T magnetic resonance scanner. After the opposing susceptibility and fractional anisotropy (FA) maps had been reconstructed, the parametric maps were spatially normalized. To evaluate the agreements of QSM-ARCS against the susceptibility source separation method using R2 and R2* maps (χ-separation) by Bland-Altman plots, the opposing susceptibility values were measured using white and deep gray matter atlases. We then evaluated the relationships between the opposing susceptibilities and FAs in the white matter and used a field-to-fiber angle to assess the fiber orientation dependencies of the opposing susceptibilities. The susceptibility maps in QSM-ARCS were successfully reconstructed without large artifacts. In the Bland-Altman analyses, the opposing QSM-ARCS susceptibility values excellently agreed with the χ-separation maps. Significant inverse and proportional correlations were observed between FA and the negative and positive susceptibilities estimated by QSM-ARCS. The fiber orientation dependencies of the negative susceptibility represented a nonmonotonic feature. Conversely, the positive susceptibility increased linearly with the fiber angle with respect to the B0 field. The QSM-ARCS could accurately estimate the opposing susceptibilities, which were identical values of χ-separation, even using gradient echo alone. The opposing susceptibilities might offer direct biomarkers for assessment of the myelin and iron content in glial cells and, through the underlying magnetic sources, provide biologic insights toward clinical transition.

APOE ɛ4 dose associates with increased brain iron and ß-amyloid via blood-brain barrier dysfunction.

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 ß-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), ß-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 ß-amyloid, through the BBB.

Delineation of prostatic calcification using quantitative susceptibility mapping: Spatial accuracy for magnetic resonance-only radiotherapy planning.

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.

Changes in Apparent Diffusion Coefficient (ADC) during Cardiac Cycle of the Brain in Idiopathic Normal Pressure Hydrocephalus Before and After Cerebrospinal Fluid Drainage.

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.

Simultaneous voxel-based magnetic susceptibility and morphometry analysis using magnetization-prepared spoiled turbo multiple gradient echo.

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 T1 -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.

Magnetic Susceptibility Associates With Dopaminergic Deficits and Cognition in Parkinson's Disease.

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.

Voxel-based quantitative susceptibility mapping in Parkinson's disease with mild cognitive impairment.

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.

Differentiation between malignant and benign musculoskeletal tumors using diffusion kurtosis imaging.

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.

Time-resolved magnetic resonance angiography as a follow-up method for visceral artery aneurysm treated with coil-embolisation.

PURPOSE: The purpose of this study is to assess the feasibility and usefulness of time-resolved magnetic resonance angiography (TR-MRA) for follow-up of visceral artery aneurysms (VAAs) after embolotherapy. MATERIAL AND METHODS: Twenty-one VAAs (11 splenic, six renal, three internal iliac, and one superior pancreaticoduodenal artery aneurysms) in 18 patients (median age, 64 years; range, 36-88 years) previously treated by embolisation with platinum coils, were evaluated. The mean size of the aneurysm was 10.5 cm3 (range, 0.3-132 cm3). Among them, 19 lesions were treated by aneurysmal packing with or without distal-to-proximal embolisation. For the remaining two lesions, distal-to-proximal embolization alone was performed. The mean observation period after embolotherapy was 35 weeks (range, 4-216). All patients underwent TR-MRA following an intravenous bolus injection of gadolinium chelate. Recanalisation was diagnosed when any portion of the aneurysmal sac was enhanced in the arterial phase. RESULTS: On TR-MRA, two lesions were diagnosed as recanalised. They were confirmed by transcatheter arteriography and re-treated by embolotherapy. For the remaining 19 lesions, there were no findings of recanalisation on TR-MRA. CONCLUSIONS: TR-MRA appears to be a feasible method for follow-up examination of VAAs treated by embolotherapy.

Shortened breath-hold contrast-enhanced MRI of the liver using a new parallel imaging technique, CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration): a comparison with conventional GRAPPA technique.

PURPOSE: We examined whether the shortened breath-hold 3-dimensional volumetric interpolated breath-hold examination (3D-VIBE) sequence for high acceleration factor (AF) using the controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) could substitute for the conventional sequence using generalized autocalibrating partially parallel acquisition (GRAPPA) in patients undergoing routine gadoxetic acid-enhanced liver MRI. MATERIALS AND METHODS: Thirty patients with clinically suspected focal liver lesions were scanned using 3D-VIBE sequences with GRAPPA with AF = 2 and AF = 4 and CAIPIRINHA with AF = 4 (acquisition times: 21, 14, and 12 s, respectively) during the hepatobiliary phase. Visual evaluations using a 3- or 5-point scale and signal-to-noise ratio (SNR) analysis were performed for the 3 sequences. RESULTS: For CAIPIRINHA with AF = 4, there was significantly less image noise in both visual evaluation and SNR analysis and fewer parallel imaging artifacts than for GRAPPA with AF = 4 (P < 0.0005); it was equal to GRAPPA with AF = 2 and had fewer motion artifacts than GRAPPA with AF = 2 and 4 (P < 0.0012). The liver edge sharpness and hepatic vessel clarity, lesion conspicuity, and overall image quality were rated significantly higher with CAIPIRINHA with AF = 4 than GRAPPA with AF = 2 and AF = 4 (P < 0.009). For GRAPPA with AF = 4, lesion conspicuity and overall image quality were rated significantly lower than for GRAPPA with AF = 2 (P < 0.012). CONCLUSION: The shortened breath-hold 3D-VIBE sequence using the new CAIPIRINHA technique with a high AF of 4 was superior to the conventional GRAPPA sequence. The shortened breath-hold sequence using GRAPPA with a high AF of 4 worsened the image quality and lesion conspicuity.

Feasibility of time-resolved MR angiography for detecting recanalization of pulmonary arteriovenous malformations treated with embolization with platinum coils.

PURPOSE: To assess the feasibility of time-resolved magnetic resonance (MR) angiography as a follow-up method after embolization for pulmonary arteriovenous malformations (PAVMs). MATERIALS AND METHODS: Evaluation of 28 PAVMs in 10 patients previously treated with embolization with platinum coils was performed. The mean observation period after embolization was 49 months. All patients underwent unenhanced chest computed tomography (CT) and time-resolved MR angiography followed by transcatheter digital subtraction angiography within 5 weeks for a definite diagnosis. Two radiologists reviewed the CT and time-resolved MR angiography findings using a blinded method. On CT, the draining veins of the PAVMs were measured before and after embolization, and shrinkage rates were calculated. On time-resolved MR angiography, recanalization was diagnosed when the draining vein or aneurysmal sac or both were enhanced in the pulmonary arterial phase. Correlations between recanalization, the shrinkage rate of the draining vein, and the diagnostic accuracies of CT and time-resolved MR angiography were assessed and compared with digital subtraction angiography. RESULTS: Five lesions could not be measured on CT because of metallic artifacts. The mean shrinkage rates of the draining vein for recanalized and occluded PAVMs were 23% ± 19 (SD) for recanalized PAVMs and 47% ± 21 for occluded PAVMs (P = .001). The sensitivity and specificity were 93% and 53%, respectively, when the shrinkage rate threshold was set to 50%. On time-resolved MR angiography, the sensitivity and specificity were 93% and 100%, respectively, for Reader 1 and 100% and 93%, respectively, for Reader 2. The κ coefficient was 0.86. CONCLUSIONS: Time-resolved MR angiography appears to be a feasible method for PAVM follow-up examinations and to provide a more accurate diagnosis of recanalization compared with unenhanced CT.

Anisotropy of the R1/T2* value dependent on white matter fiber orientation with respect to the B0 field.

The R1 (1/T1) map divided by the T2* map (R1/T2* map) draws attention as a high-resolution myelin-related map. However, both R1 and R2* (1/T2*) values demonstrate anisotropy dependent on the white matter (WM) fiber orientation with respect to the static magnetic (B0) field. Therefore, this study primarily aimed to investigate the comprehensive impact of these angular-dependent anisotropies on the R1/T2* value. This study enrolled 10 healthy human volunteers (age = 25 ± 1.3) on the 3.0 T MRI system. For R1/T2* map calculation, whole brain R1 and T2* maps were repeatedly obtained in three head tilt positions by magnetization-prepared two rapid gradient echoes and multiple spoiled gradient echo sequences, respectively. Afterward, all maps were spatially normalized and registered to the Johns Hopkins University WM atlas. R1/T2*, R1, and R2* values were binned for fiber orientation related to the B0 field, which was estimated from diffusion-weighted echo-planar imaging data with 3° intervals, to investigate angular-dependent anisotropies in vivo. A larger change in the R1/T2* value in the global WM region as a function of fiber orientation with respect to the B0 field was observed compared to the R1 and R2* values alone. The minimum R1/T2* value at the near magic-angle range was 18.86% lower than the maximum value at the perpendicular angle range. Furthermore, R1/T2* values in the corpus callosum tract and the right and left cingulum cingulate gyrus tracts changed among the three head tilt positions due to fiber orientation changes. In conclusion, the R1/T2* value demonstrates distinctive and complicated angular-dependent anisotropy indicating the trends of both R1 and R2* values and may provide supplemental information for detecting slight changes in the microstructure of myelin and axons.

Alterations in subcortical magnetic susceptibility and disease-specific relationship with brain volume in major depressive disorder and schizophrenia.

Quantitative susceptibility mapping is a magnetic resonance imaging technique that measures brain tissues' magnetic susceptibility, including iron deposition and myelination. This study examines the relationship between subcortical volume and magnetic susceptibility and determines specific differences in these measures among patients with major depressive disorder (MDD), patients with schizophrenia, and healthy controls (HCs). This was a cross-sectional study. Sex- and age- matched patients with MDD (n = 49), patients with schizophrenia (n = 24), and HCs (n = 50) were included. Magnetic resonance imaging was conducted using quantitative susceptibility mapping and T1-weighted imaging to measure subcortical susceptibility and volume. The acquired brain measurements were compared among groups using analyses of variance and post hoc comparisons. Finally, a general linear model examined the susceptibility-volume relationship. Significant group-level differences were found in the magnetic susceptibility of the nucleus accumbens and amygdala (p = 0.045). Post-hoc analyses indicated that the magnetic susceptibility of the nucleus accumbens and amygdala for the MDD group was significantly higher than that for the HC group (p = 0.0054, p = 0.0065, respectively). However, no significant differences in subcortical volume were found between the groups. The general linear model indicated a significant interaction between group and volume for the nucleus accumbens in MDD group but not schizophrenia or HC groups. This study showed susceptibility alterations in the nucleus accumbens and amygdala in MDD patients. A significant relationship was observed between subcortical susceptibility and volume in the MDD group's nucleus accumbens, which indicated abnormalities in myelination and the dopaminergic system related to iron deposition.

Contributions of blood-brain barrier imaging to neurovascular unit pathophysiology of Alzheimer's disease and related dementias.

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 ß-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.

Relationship between brain iron dynamics and blood-brain barrier function during childhood: a quantitative magnetic resonance imaging study.

BACKGROUND: Mounting evidence suggests that the blood-brain barrier (BBB) plays an important role in the regulation of brain iron homeostasis in normal brain development, but these imaging profiles remain to be elucidated. We aimed to establish a relationship between brain iron dynamics and BBB function during childhood using a combined quantitative magnetic resonance imaging (MRI) to depict both physiological systems along developmental trajectories. METHODS: In this single-center prospective study, consecutive outpatients, 2-180 months of age, who underwent brain MRI (3.0-T scanner; Ingenia; Philips) between January 2020 and January 2021, were included. Children with histories of preterm birth or birth defects, abnormalities on MRI, and diagnoses that included neurological diseases during follow-up examinations through December 2022 were excluded. In addition to clinical MRI, quantitative susceptibility mapping (QSM; iron deposition measure) and diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL; BBB function measure) were acquired. Atlas-based analyses for QSM and DP-pCASL were performed to investigate developmental trajectories of regional brain iron deposition and BBB function and their relationships. RESULTS: A total of 78 children (mean age, 73.8 months ± 61.5 [SD]; 43 boys) were evaluated. Rapid magnetic susceptibility progression in the brain (Δsusceptibility value) was observed during the first two years (globus pallidus, 1.26 ± 0.18 [× 10- 3 ppm/month]; substantia nigra, 0.68 ± 0.16; thalamus, 0.15 ± 0.04). The scattergram between the Δsusceptibility value and the water exchange rate across the BBB (kw) divided by the cerebral blood flow was well fitted to the sigmoidal curve model, whose inflection point differed among each deep gray-matter nucleus (globus pallidus, 2.96-3.03 [mL/100 g]-1; substantia nigra, 3.12-3.15; thalamus, 3.64-3.67) in accordance with the regional heterogeneity of brain iron accumulation. CONCLUSIONS: The combined quantitative MRI study of QSM and DP-pCASL for pediatric brains demonstrated the relationship between brain iron dynamics and BBB function during childhood. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000039047, registered January 6, 2020.

Three-compartment spectral diffusion analysis for breast cancer magnetic resonance imaging.

RATIONALE AND OBJECTIVES: To examine the diagnostic performance of a three-compartment diffusion model with the fixed cut-off diffusion coefficient (D) using magnetic resonance spectral diffusion analysis for differentiating between invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) and compare the conventional apparent D (ADC), and mean kurtosis (MK), with the tissue D (DIVIM), perfusion D (D*IVIM), and perfusion fraction (fIVIM) calculated by conventional intravoxel incoherent motion. PATIENTS AND METHODS: This retrospective study included women who underwent breast MRI with eight b-value diffusion-weighted imaging between February 2019 and March 2022. Spectral diffusion analysis was performed; very-slow, cellular, and perfusion compartments were defined using cut-off Ds of 0.1 × 10-3 and 3.0 × 10-3 mm2/s (static water D). The mean D (Ds, Dc, Dp, respectively) and fraction F (Fs, Fc, Fp, respectively) for each compartment were calculated. ADC and MK values were also calculated; receiver operating characteristic analyses were performed. RESULTS: Histologically confirmed 132 ICD and 62 DCIS (age range 31-87 [53 ± 11] years) were evaluated. The areas under the curve (AUCs) for ADC, MK, DIVIM, D*IVIM, fIVIM, Ds, Dc, Dp, Fs, Fc, and Fp were 0.77, 0.72, 0.77, 0.51, 0.67, 0.54, 0.78, 0.51, 0.57, 0.54, and 0.57, respectively. The AUCs for the model combining very-slow and cellular compartments and the model combining the three compartments were 0.81 each, slightly and significantly higher than for ADC, DIVIM, and Dc (P = 0.09-0.14); and MK (P < 0.05), respectively. CONCLUSION: Three-compartment model analysis using the diffusion spectrum accurately differentiated IDC from DCIS; however, it was not superior to ADC and DIVIM. The diagnostic performance of MK was lower than that of the three-compartment model.

Voxel-Based and Surface-Based Morphometry Analysis in Patients with Pathologically Confirmed Argyrophilic Grain Disease and Alzheimer's Disease.

BACKGROUND: Due to clinicoradiological similarities, including amnestic cognitive impairment and limbic atrophy, differentiation of argyrophilic grain disease (AGD) from Alzheimer's disease (AD) is often challenging. Minimally invasive biomarkers, especially magnetic resonance imaging (MRI), are valuable in routine clinical practice. Although it is necessary to explore radiological clues, morphometry analyses using new automated analytical methods, including whole-brain voxel-based morphometry (VBM) and surface-based morphometry (SBM), have not been sufficiently investigated in patients with pathologically confirmed AGD and AD. OBJECTIVE: This study aimed to determine the volumetric differences in VBM and SBM analyses between patients with pathologically confirmed AGD and AD. METHODS: Eight patients with pathologically confirmed AGD with a lower Braak neurofibrillary tangle stage (

Assessing white matter microstructural changes in idiopathic normal pressure hydrocephalus using voxel-based R2* relaxometry analysis.

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.

Brain Abnormalities in Becker Muscular Dystrophy: Evaluation by Voxel-Based DTI and Morphometric Analysis.

BACKGROUND AND PURPOSE: Although various neuropsychological problems in Becker muscular dystrophy have attracted attention, there have been few related neuroimaging studies. We investigated brain abnormalities in patients with Becker muscular dystrophy using 3D T1WI and DTI. MATERIALS AND METHODS: MR images were obtained for 30 male patients and 30 age-matched healthy male controls. We classified patients into Dp140+ and Dp140- subgroups based on their predicted dystrophin Dp140 isoform expression and performed voxel-based comparisons of gray and white matter volumes and DTI metrics among the patients, patient subgroups, and controls. ROI-based DTI analyses were also performed. RESULTS: Significantly decreased fractional anisotropy was observed in the left planum temporale and right superior parietal lobule compared between the Becker muscular dystrophy and control groups. In the Dp140- subgroup, decreased fractional anisotropy was observed in the left planum temporale, but no significant changes were seen in the Dp140+ subgroup. The ROI-based analysis obtained the same results. No significant differences were evident in the gray or white matter volumes or the DTI metrics other than fractional anisotropy between the groups. CONCLUSIONS: A DTI metric analysis is useful to detect white-matter microstructural abnormalities in Becker muscular dystrophy that may be affected by the Dp140 isoform expression.