Unpaired deep learning for pharmacokinetic parameter estimation from dynamic contrast-enhanced MRI without AIF measurements.

DCE-MRI provides information about vascular permeability and tissue perfusion through the acquisition of pharmacokinetic parameters. However, traditional methods for estimating these pharmacokinetic parameters involve fitting tracer kinetic models, which often suffer from computational complexity and low accuracy due to noisy arterial input function (AIF) measurements. Although some deep learning approaches have been proposed to tackle these challenges, most existing methods rely on supervised learning that requires paired input DCE-MRI and labeled pharmacokinetic parameter maps. This dependency on labeled data introduces significant time and resource constraints and potential noise in the labels, making supervised learning methods often impractical. To address these limitations, we present a novel unpaired deep learning method for estimating pharmacokinetic parameters and the AIF using a physics-driven CycleGAN approach. Our proposed CycleGAN framework is designed based on the underlying physics model, resulting in a simpler architecture with a single generator and discriminator pair. Crucially, our experimental results indicate that our method does not necessitate separate AIF measurements and produces more reliable pharmacokinetic parameters than other techniques.

Sandwich spatial saturation for neuromelanin-sensitive MRI: Development and multi-center trial.

Neuromelanin (NM)-sensitive MRI using a magnetization transfer (MT)-prepared T1-weighted sequence has been suggested as a tool to visualize NM contents in the brain. In this study, a new NM-sensitive imaging method, sandwichNM, is proposed by utilizing the incidental MT effects of spatial saturation RF pulses in order to generate consistent high-quality NM images using product sequences. The spatial saturation pulses are located both superior and inferior to the imaging volume, increasing MT weighting while avoiding asymmetric MT effects. When the parameters of the spatial saturation were optimized, sandwichNM reported a higher NM contrast ratio than those of conventional NM-sensitive imaging methods with matched parameters for comparability with sandwichNM (SandwichNM: 23.6 ± 5.4%; MT-prepared TSE: 20.6 ± 7.4%; MT-prepared GRE: 17.4 ± 6.0%). In a multi-vendor experiment, the sandwichNM images displayed higher means and lower standard deviations of the NM contrast ratio across subjects in all three vendors (SandwichNM vs. MT-prepared GRE; Vendor A: 28.4 ± 1.5% vs. 24.4 ± 2.8%; Vendor B: 27.2 ± 1.0% vs. 13.3 ± 1.3%; Vendor C: 27.3 ± 0.7% vs. 20.1 ± 0.9%). For each subject, the standard deviations of the NM contrast ratio across the vendors were substantially lower in SandwichNM (SandwichNM vs. MT-prepared GRE; subject 1: 1.5% vs. 8.1%, subject 2: 1.1 % vs. 5.1%, subject 3: 0.9% vs. 4.0%, subject 4: 1.1% vs. 5.3%), demonstrating consistent contrasts across the vendors. The proposed method utilizes product sequences, requiring no alteration of a sequence and, therefore, may have a wide practical utility in exploring the NM imaging.

Choroid Plexus Volume and Permeability at Brain MRI within the Alzheimer Disease Clinical Spectrum.

Background Mounting evidence suggests that the choroid plexus (CP) plays an important role in the pathophysiology of Alzheimer disease (AD), but its imaging profile in cognitive impairment remains unclear. Purpose To evaluate CP volume, permeability, and susceptibility by using MRI in patients at various stages of cognitive impairment. Materials and Methods This retrospective study evaluated patients with cognitive symptoms who underwent 3.0-T MRI of the brain, including dynamic contrast-enhanced (DCE) imaging and quantitative susceptibility mapping (QSM), between January 2013 and May 2020. CP volume was automatically segmented using three-dimensional T1-weighted sequences; the volume transfer constant (ie, Ktrans) and fractional plasma volume (ie, Vp) were determined using DCE MRI, and susceptibility was assessed using QSM. The effects of CP volume, expressed as the ratio to intracranial volume, on cognition were evaluated using multivariable linear regression adjusted for age, sex, education, apolipoprotein E ε4 allele status, and volumetric measures. Results A total of 532 patients with cognitive symptoms (mean age, 72 years ± 9 [SD]; 388 women) were included: 78 with subjective cognitive impairment (SCI), 158 with early mild cognitive impairment (MCI), 149 with late MCI, and 147 with AD. Among these, 132 patients underwent DCE MRI and QSM. CP volume was greater in patients at more severe stages (ratio of intracranial volume × 103: 0.9 ± 0.3 for SCI, 1.0 ± 0.3 for early MCI, 1.1 ± 0.3 for late MCI, and 1.3 ± 0.4 for AD; P < .001). Lower Ktrans (r = -0.19; P = .03) and Vp (r = -0.20; P = .02) were negatively associated with CP volume; susceptibility was not (r = 0.15; P = .10). CP volume was negatively associated with memory (B = -0.67; standard error of the mean [SEM], 0.21; P = .01), executive function (B = -0.90; SEM, 0.31; P = .01), and global cognition (B = -0.82; SEM, 0.32; P = .01). Conclusion Among patients with cognitive symptoms, larger choroid plexus volume was associated with severity of cognitive impairment in the Alzheimer disease spectrum. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Chiang in this issue.

Contrast-Enhanced Fluid-Attenuated Inversion Recovery in Neuroimaging: A Narrative Review on Clinical Applications and Technical Advances.

While contrast-enhanced fluid-attenuated inversion recovery (FLAIR) has long been regarded as an adjunct sequence to evaluate leptomeningeal disease in addition to contrast-enhanced T1-weighted imaging, it is gradually being used for more diverse pathologies beyond leptomeningeal disease. Contrast-enhanced FLAIR is known to be highly sensitive to low concentrations of gadolinium within the fluid. Accordingly, recent research has suggested the potential utility of contrast-enhanced FLAIR in various kinds of disease, such as Meniere's disease, seizure, stroke, traumatic brain injury, and brain metastasis, in addition to being used for visualizing glymphatic dysfunction. However, its potential applications have been reported sporadically in an unorganized manner. Furthermore, the exact mechanism for its superior sensitivity to low concentrations of gadolinium has not been fully understood. Rapidly developing magnetic resonance technology and unoptimized parameters for FLAIR may challenge its accurate application in clinical practice. This review provides the fundamental mechanism of contrast-enhanced FLAIR, systematically describes its current and potential clinical application, and elaborates on technical considerations for its optimization. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 5.

Magnetic susceptibility in the deep gray matter may be modulated by apolipoprotein E4 and age with regional predilections: a quantitative susceptibility mapping study.

PURPOSE: To examine the relationship between apolipoprotein E gene (APOE) mutation status and iron accumulation in the deep gray matter of subjects with cognitive symptoms using quantitative susceptibility mapping (QSM). METHODS: A total of 105 patients with cognitive symptoms were enrolled. QSM data were generated from 3D gradient-echo data using an STI Suite algorithm. A region of interest-based analysis with QSM was performed in the deep gray matter. Differences between APOE4 carriers and non-carriers were assessed by analysis of covariance. Multiple regression analysis was performed to identify the factors associated with magnetic susceptibility. RESULTS: Clinical characters such as age, education, MMSE, vascular risk burden, and systolic blood pressure differ between APOE4 carrier and non-carrier groups. The APOE4 carrier group had higher magnetic susceptibility values than the non-carrier group, with significant differences in the caudate (p = 0.004), putamen (p < 0.0001), and globus pallidus (p < 0.0001) which imply higher iron accumulation. In a multiple regression analysis, APOE4 status was found to be a predictor of magnetic susceptibility value in the globus pallidus (p = 0.03); age for magnetic susceptibility value in the caudate nucleus (p = 0.0064); and age and hippocampal atrophy for magnetic susceptibility value in the putamen (p < 0.05). CONCLUSION: Our study demonstrates that magnetic susceptibility in globus pallidus is related to APOE4 status while those of caudate and putamen are related to other factors including age. It suggests that brain iron accumulation in the deep gray matter is modulated by APOE4 and age with differential regional predilection.

Sarcopenia in patients with dementia: correlation of temporalis muscle thickness with appendicular muscle mass.

Cognitive decline is one of the most relevant signs of sarcopenia; however, it is challenging to perform tests for sarcopenia in patients with dementia. In a recent study, temporalis muscle thickness (TMT), an alternative to appendicular muscle mass (ASM), was found to be a valid index for screening sarcopenia. This study aimed to determine whether TMT correlates with ASM and evaluate the relationship between TMT and cognitive function in dementia patients. We recruited patients with a complaint of memory loss who visited the Memory Clinic of Konkuk University Medical Center between November 2014 and December 2020. Patients with probable Alzheimer's disease (AD) without weakness were included. TMT was measured on axial T1-weighted magnetic resonance (MR) images, perpendicular to the long axis of the temporal muscle, at the orbital roof level. ASM was measured using body dual-energy X-ray absorptiometry (DXA). It was calculated as the sum of lean soft tissue mass in the arms and legs, and the value by ASM divided by height squared was used. Inter-rater reliability and intra-rater reliability were good and excellent, respectively. We found a correlation between TMT and skeletal ASM, which was obtained from cranial MR images and DXA, respectively (r = 0.379, p = 0.001). TMT was negatively correlated with age (r = - 0.296, p = 0.014) and positively correlated with body mass index (BMI) (r = 0.303, p = 0.012). Additionally, TMT was correlated with MMSE (r = 0.350, p = 0.003). After adjusting for educational years, there was still a correlation between TMT and MMSE (r = 0.256, p = 0.038). This study demonstrated that TMT correlates with ASM and cognitive function in patients with dementia. Measuring TMT using cranial MR images could help diagnose sarcopenia accessibly and assess cognitive function in patients with dementia.

Time optimization of gadobutrol-enhanced brain MRI for metastases and primary tumors using a dynamic contrast-enhanced imaging.

BACKGROUND: Recent advances in rapid imaging techniques necessitate the reconsideration of the optimal imaging delay time for contrast-enhanced T1-weighted imaging. The aim of our study was to determine the optimal contrast-enhanced T1-weighted imaging delay time from the obtained time-signal intensity curve (TIC) using gadobutrol in patients with brain metastases, primary brain tumors, and meningiomas. METHODS: This prospective study enrolled 78 patients with brain metastases (n = 39), primary brain tumors (n = 22), or meningiomas (n = 17) who underwent 7-min dynamic contrast-enhanced imaging with single-dose gadobutrol. Based on the time-to-peak (TTP) derived from the TIC, we selected four different time points for analysis. Lesion conspicuity, enhanced rate (ER) and contrast rate (CR) of 116 index lesions were evaluated. Statistical comparisons were made for the four different time points using the Friedman test. RESULTS: Maximum TTP (305.20 ± 63.47 s) was similar across all three groups (p = 0.342). Lesion conspicuity, CR and ER increased over time in all index lesions; however, no significant difference between the 5- and 7-min images was observed. The longest diameter in all groups differed significantly among time points (p < 0.001); the perpendicular diameter did not differ between the 5- and 7-min images. CONCLUSIONS: Maximum contrast enhancement and lesion conspicuity was achieved 5-7 min after a single gadobutrol injection for brain metastases detection and for primary brain tumor/meningioma evaluation. Acquiring images 5 min after gadobutrol injection is the optimal timing for brain tumor detection during MRI work-up.

Artificial neural network for multi-echo gradient echo-based myelin water fraction estimation.

PURPOSE: To demonstrate robust myelin water fraction (MWF) mapping using an artificial neural network (ANN) with multi-echo gradient-echo (GRE) signal. METHODS: Multi-echo gradient-echo signals simulated with a three-pool exponential model were used to generate the training data set for the ANN, which was designed to yield the MWF. We investigated the performance of our proposed ANN for various conditions using both numerical simulations and in vivo data. Simulations were conducted with various SNRs to investigate the performance of the ANN. In vivo data with high spatial resolutions were applied in the analyses, and results were compared with MWFs derived by the nonlinear least-squares algorithm using a complex three-pool exponential model. RESULTS: The network results for the simulations show high accuracies against noise compared with nonlinear least-squares MWFs: RMS-error value of 5.46 for the nonlinear least-squares MWF and 3.56 for the ANN MWF at an SNR of 150 (relative gain = 34.80%). These effects were also found in the in vivo data, with reduced SDs in the region-of-interest analyses. These effects of the ANN demonstrate the feasibility of acquiring high-resolution myelin water images. CONCLUSION: The simulation results and in vivo data suggest that the ANN facilitates more robust MWF mapping in multi-echo gradient-echo sequences compared with the conventional nonlinear least-squares method.

Ultrafast Infrared Photoresponse from Heavily Hydrogen-Doped VO2 Single Crystalline Nanoparticles.

Infrared photodetectors are sought for diverse applications and their performance relies on photoactive materials and photocurrent generation mechanisms. Here, we fabricate IR photodetectors with heavily hydrogen-doped VO2 (i.e., HVO2) single-crystalline nanoparticles which show two orders greater resistivities than pure VO2. The I-V plots obtained under IR light irradiation are expressed by space charge limited current mechanism and the increase in photocurrent occurs due to the increase in the number of photoinduced trap sites. This phenomenon remarkably improves the key parameters at λ = 780 nm of high responsivity of 35280 A/W, high detectivity of 1.12 × 1013 Jones, and strikingly fast response times of 0.6-2.5 ns, that is, 3 orders of magnitude faster than the best records of two-dimensional structures and heterostructures. Density functional theory calculations illustrate that the generation of photoinduced trap sites is attributed to the movement of hydrogen atoms to less stable interstitial sites in VO2 under light exposure.

Sex-Related Differences in Regional Blood-Brain Barrier Integrity in Non-Demented Elderly Subjects.

The role of the blood-brain barrier (BBB) breakdown has been recognized as being important in Alzheimer's disease pathogenesis. We aimed to evaluate whether regional BBB integrity differed according to sex and whether differences in BBB integrity changed as a consequence of aging or cognitive decline, using dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI). In total, 75 participants with normal cognition (NC) or mild cognitive impairment (MCI) underwent cognitive assessments and MRI examination including DCE-MRI. Regional Ktrans was calculated in cortical regions and the Patlak permeability model was used to calculate BBB permeability (Ktrans, min-1). Females had a lower median Ktrans in the cingulate and occipital cortices. In the "older old" group, sex differences in Ktrans were only observed in the occipital cortex. In the MCI group, sex differences in Ktrans were only observed in the occipital cortex. Age was the only predictor of cognitive assessment scores in the male MCI group; however, educational years and Ktrans in the occipital cortex could predict cognitive scores in the female MCI group. Our study revealed that females may have better BBB integrity in cingulate and occipital cortices. We also found that sex-related differences in BBB integrity are attenuated with aging or cognitive decline.

Myelin loss in white matter hyperintensities and normal-appearing white matter of cognitively impaired patients: a quantitative synthetic magnetic resonance imaging study.

OBJECTIVES: White matter hyperintensities (WMHs) are implicated in the etiology of dementia. The underlying pathology of WMHs involves myelin and axonal loss due to chronic ischemia. We investigated myelin loss in WMHs and normal-appearing white matter (NAWM) in patients with various degrees of cognitive impairment using quantitative synthetic magnetic resonance imaging (MRI). METHODS: We studied 99 consecutive patients with cognitive complaints who underwent 3 T brain MRI between July 2016 and August 2017. Myelin partial volume maps were generated with synthetic MRI. Region-of-interest-based analysis was performed on these maps to compare the myelin partial volumes of NAWM and periventricular and deep WMHs. The effects of myelin partial volume of NAWMs on clinical cognitive function were evaluated using multivariate linear regression analysis. RESULTS: WMHs were present in 30.3% of patients. Myelin partial volume in NAWM was lower in patients with WMHs than in those without (37.5 ± 2.7% vs. 39.9 ± 2.4%, p < 0.001). In patients with WMHs, myelin partial volume was highest in NAWMs (median [interquartile range], 37.2% [35.5-39.0%]), followed by deep WMHs (7.2% [3.2-10.5%]) and periventricular WMHs (2.1% [1.1-3.9%], p < 0.001). After adjusting for sex and education years, myelin partial volume in NAWMs was associated with the Clinical Dementia Rating Scale Sum of Box (ß = -0.189 [95% CI, -0.380 to -0.012], p = 0.031). CONCLUSION: Myelin loss occurs in both NAWM and WMHs of cognitively impaired patients. Synthetic MRI-based myelin quantification may be a useful imaging marker of cognitive dysfunction in patients with cognitive complaints. KEY POINTS: • Quantitative synthetic MRI allows simultaneous acquisition of conventional MRI and myelin quantification without additional scanning time. • Normal-appearing and hyperintense white matter demonstrate myelin loss in cognitively impaired patients. • This myelin loss partially explains cognitive dysfunction in patients with cognitive complaints.

Muscle Strength Is Independently Related to Brain Atrophy in Patients with Alzheimer's Disease.

BACKGROUND/AIMS: Alzheimer's disease (AD) is the most common cause of dementia worldwide. Interestingly, muscle mass (MM) and muscle strength (MS) are related to AD. In addition to the muscle profile, brain atrophy is also a prominent feature of AD. There is substantial evidence showing an association between muscle profile and dementia, but the role of the muscle profile and cerebral cortical atrophy within this association is less well understood. The objective of this study was to determine if there is any association between muscle profile and brain regional volume in AD. A secondary objective was to determine whether this relationship continues as the clinical stage of AD progresses. METHODS: We recruited 28 patients with probable AD without weakness. We assessed the patients' basic demographic characteristics, Mini-Mental State Examination score, and brain magnetic resonance images. MM was measured using body dual-energy X-ray absorptiometry. MS was assessed in Nm/kg with an isokinetic knee extensor using an isokinetic device at an angular velocity of 60°/s. An automatic analysis program was used for brain regional volumetric measurements. Dementia was divided into two stages: mild and moderate. RESULTS: MS was related to left hippocampal volume ratio. After adjusting for age and cognitive status, the relationship remained. MS did not demonstrate any relationship to any brain regional volume ratio in the mild stage; however, in the moderate stage, it was positively related to both the right and the left hippocampal volume ratio. CONCLUSIONS: Our findings imply a shared underlying pathology relating MS and brain volume and suggest cognitive functional declines through the muscle-brain axis. Further longitudinal studies are needed to find possible and related causes of reduced MS and cortical atrophy in patients with dementia.

Brain-State Extraction Algorithm Based on the State Transition (BEST): A Dynamic Functional Brain Network Analysis in fMRI Study.

Spatial pattern of the brain network changes dynamically. This change is closely linked to the brain-state transition, which vary depending on a dynamic stream of thoughts. To date, many dynamic methods have been developed for decoding brain-states. However, most of them only consider changes over time, not the brain-state transition itself. Here, we propose a novel dynamic functional connectivity analysis method, brain-state extraction algorithm based on state transition (BEST), which constructs connectivity matrices from the duration of brain-states and decodes the proper number of brain-states in a data-driven way. To set the duration of each brain-state, we detected brain-state transition time-points using spatial standard deviation of the brain activity pattern that changes over time. Furthermore, we also used Bayesian information criterion to the clustering method to estimate and extract the number of brain-states. Through validations, it was proved that BEST could find brain-state transition time-points and could estimate the proper number of brain-states without any a priori knowledge. It has also shown that BEST can be applied to resting state fMRI data and provide stable and consistent results.

Motor cortex hypointensity on susceptibility-weighted imaging: a potential imaging marker of iron accumulation in patients with cognitive impairment.

PURPOSE: To assess the prevalence and characteristics of motor cortex hypointensity on 3-T susceptibility-weighted imaging (SWI) in patients with cognitive impairment and examine its clinical significance. METHODS: The institutional review board approved this retrospective study and waived the requirement for informed consent. A total of 127 patients with a clinical diagnosis of probable Alzheimer's disease (AD) (n = 32) or mild cognitive impairment (MCI) (n = 95) and 127 age- and sex-matched control subjects underwent 3-T brain magnetic resonance imaging. SWI was analyzed for both subjective visual scoring and the quantitative estimation of phase shift in the posterior bank of the motor cortex. A multivariate logistic regression analysis was performed to identify clinical and imaging variables associated with motor cortex hypointensity on SWI. RESULTS: Motor cortex hypointensity on SWI was observed in 94/127 cognitively impaired patients (74.0%) and 72/127 control subjects (56.7%) (p = 0.004). Age was the only variable that was significantly associated with motor cortex hypointensity in patients with cognitive impairment (odds ratio, 1.15; 95% confidence interval, 1.065-1.242; p < 0.001). The quantitative analysis confirmed a significant increase in phase shifting in the posterior bank of the motor cortex in patients with positive motor cortex hypointensity on SWI (p < 0.001). CONCLUSION: Motor cortex hypointensity on SWI was more frequently found in patients with cognitive impairment than in age-matched controls and was positively associated with age. Thus, it may be a potential imaging marker of iron accumulation in patients with MCI or AD.

Role of Muscle Profile in Alzheimer's Disease: A 3-Year Longitudinal Study.

INTRODUCTION: Many factors are known to affect the rate of cognitive decline; however, studies on clinical outcomes are rare. Muscle profile and their relationship to dementia trajectories have not been extensively investigated. We investigated factors that affect the rate of clinical decline and the usefulness of muscle profiles for predicting the clinical outcomes of patients with Alzheimer's dementia (AD). OBJECTIVE: Sixty-nine subjects with probable AD were included and several factors that are known to affect the rate of cognitive decline were evaluated. METHODS: Over a period of 3 years, each subject received an annual evaluation that included a clinical interview and an assessment of their cognitive status as measured by a clinical dementia rating-sum of boxes (CDR-SOB) score. Linear mixed-effects models were used to test for associations between each factor and the -CDR-SOB score over time. These analyses were repeated in a multivariate linear mixed-effects model after adjusting the covariates. RESULTS: Age, diabetes mellitus, and baseline dementia severity were identified as potential covariates that influence clinical progression. However, a subject's muscle profile was not found to predict dementia progression. CONCLUSIONS: We expect that early screening and intervention, as well as new drugs with mechanisms of action similar to those of antidiabetic medications, will help patients with dementia maintain their clinical status.

Diagnostic Efficacy of Structural MRI in Patients With Mild-to-Moderate Alzheimer Disease: Automated Volumetric Assessment Versus Visual Assessment.

OBJECTIVE: The purpose of this study was to compare the diagnostic efficacies of an automated volumetric assessment tool and visual assessment in the evaluation of medial temporal lobar atrophy in mild-to-moderate Alzheimer disease (AD). MATERIALS AND METHODS: This retrospective study included 30 patients with mild-to-moderate AD and 25 age-matched healthy control subjects undergoing MRI with a 3D fast spoiled gradient recalled-echo sequence at 3 T. The images were processed with fully automated volumetric analysis software. To assess medial temporal lobe (MTL) atrophy, two MTL indexes, which took into account the volumes of the hippocampus and the inferior lateral ventricle, were calculated with the automated volumetric assessment software. In addition, two neuroradiologists assessed MTL atrophy visually using the Scheltens scale. ROC curve analysis was used to compare the diagnostic performances of the two methods. The weighted kappa statistic was used to assess the intrarater and interrater reliability of visual inspection. RESULTS: The automated volumetric assessment tool had moderate sensitivity (63.3%) and high specificity (100%) in differentiating patients with mild-to-moderate AD from control subjects. Visual inspection showed sensitivity of 63.3% and specificity of 92.0%. The diagnostic performance was not significantly different between the two methods (p = 0.536-0.906). Intraobserver reliability for visual inspection was 0.858 and 0.902 for the two reviewers, and interobserver reliability was 0.692-0.780. CONCLUSION: Both the automated volumetric assessment tool and visual inspection can be used to evaluate MTL atrophy and differentiate patients with AD from healthy individuals with good diagnostic accuracy. Thus, the automated tool can be a useful and efficient adjunct in clinical practice for evaluating MTL atrophy in the diagnosis of AD.

Quantification of myelin in children using multiparametric quantitative MRI: a pilot study.

PURPOSE: The purpose of this study was to evaluate the usefulness of multiparametric quantitative MRI for myelination quantification in children. METHODS: We examined 22 children (age 0-14 years) with multiparametric quantitative MRI. The total volume of myelin partial volume (Msum), the percentage of Msum within the whole brain parenchyma (Mbpv), and the percentage of Msum within the intracranial volume (Micv) were obtained. Four developmental models of myelin maturation (the logarithmic, logistic, Gompertz, and modified Gompertz models) were examined to find the most representative model of the three parameters. We acquired myelin partial volume values in different brain regions and assessed the goodness of fit for the models. RESULTS: The ranges of Msum, Mbpv, and Micv were 0.8-160.9 ml, 0.2-13%, and 0.0-11.6%, respectively. The Gompertz model was the best fit for the three parameters. For developmental model analysis of myelin partial volume in each brain region, the Gompertz model was the best-fit model for pons (R 2 = 74.6%), middle cerebeller peduncle (R 2 = 76.4%), putamen (R2 = 95.8%), and centrum semiovale (R 2 = 77.7%). The logistic model was the best-fit model for the genu and splenium of the corpus callosum (R 2 = 79.7-93.6%), thalamus (R 2 = 81.7%), and frontal, parietal, temporal, and occipital white matter (R 2 = 92.5-96.5%). CONCLUSIONS: Multiparametric quantitative MRI depicts the normal developmental pattern of myelination in children. It is a potential tool for research studies on pediatric brain development evaluation.

Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion.

BACKGROUND AND PURPOSE: Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion. METHODS: Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury. RESULTS: Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration. CONCLUSIONS: White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia.