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.

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.

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.

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.

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.

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.

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 (

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.

Effects of a new speech support application on intensive speech therapy and changes in functional brain connectivity in patients with post-stroke aphasia.

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.

Noncontrast time-resolved pulmonary magnetic resonance angiography with consecutive beam saturation pulse and variable flip angles using three-dimensional fast spin echo: A preliminary study.

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.

Quantitative susceptibility mapping as an imaging biomarker for Alzheimer's disease: The expectations and limitations.

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 ß-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 ß-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 ß-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.

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.

Penumbra Detection With Oxygen Extraction Fraction Using Magnetic Susceptibility in Patients With Acute Ischemic Stroke.

BACKGROUND: 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. MATERIALS AND METHODS: This prospective imaging study included 21 patients with large anterior circulation vessel occlusion who were admitted <24 h after stroke onset and 21 age-matched healthy controls. We identified the ischemic penumbra as the region with a Tmax of >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. RESULTS: 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 >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 (r = 0.636, 95% CI: 0.059 to 0.895, P = 0.035) and inversely correlated with the 30-day change in the National Institutes of Health Stroke Scale scores (r = -0.624, 95% CI: -0.891 to -0.039, P = 0.041). CONCLUSION: 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.

R2* relaxometry analysis for mapping of white matter alteration in Parkinson's disease with mild cognitive impairment.

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.

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.

Machine learning trained with quantitative susceptibility mapping to detect mild cognitive impairment in Parkinson's disease.

BACKGROUND: Cognitive decline is commonly observed in Parkinson's disease (PD). Identifying PD with mild cognitive impairment (PD-MCI) is crucial for early initiation of therapeutic interventions and preventing cognitive decline. OBJECTIVE: We aimed to develop a machine learning model trained with magnetic susceptibility values based on the multi-atlas label-fusion method to classify PD without dementia into PD-MCI and normal cognition (PD-CN). METHODS: This multicenter observational cohort study retrospectively reviewed 61 PD-MCI and 59 PD-CN cases for the internal validation cohort and 22 PD-MCI and 21 PD-CN cases for the external validation cohort. The multi-atlas method parcellated the quantitative susceptibility mapping (QSM) images into 20 regions of interest and extracted QSM-based magnetic susceptibility values. Random forest, extreme gradient boosting, and light gradient boosting were selected as machine learning algorithms. RESULTS: All classifiers demonstrated substantial performances in the classification task, particularly the random forest model. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve for this model were 79.1%, 77.3%, 81.0%, and 0.78, respectively. The QSM values in the caudate nucleus, which were important features, were inversely correlated with the Montreal Cognitive Assessment scores (right caudate nucleus: r = -0.573, 95% CI: -0.801 to -0.298, p = 0.003; left caudate nucleus: r = -0.659, 95% CI: -0.894 to -0.392, p < 0.001). CONCLUSIONS: Machine learning models trained with QSM values successfully classified PD without dementia into PD-MCI and PD-CN groups, suggesting the potential of QSM values as an auxiliary biomarker for early evaluation of cognitive decline in patients with PD.

T-staging of rectal cancer: Utility of single-shot turbo spin-echo diffusion-weighted imaging with T2-weighted images and fusion images.

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.

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.