Deep Learning-Driven Transformation: A Novel Approach for Mitigating Batch Effects in Diffusion MRI Beyond Traditional Harmonization.

BACKGROUND: "Batch effect" in MR images, due to vendor-specific features, MR machine generations, and imaging parameters, challenges image quality and hinders deep learning (DL) model generalizability. PURPOSE: We aim to develop a DL model using contrast adjustment and super-resolution to reduce diffusion-weighted images (DWIs) diversity across magnetic field strengths and imaging parameters. STUDY TYPE: Retrospective. SUBJECTS: The DL model was built using an open dataset from one individual. The MR machine identification model was trained and validated on a dataset of 1134 adults (54% females, 46% males), with 1050 subjects showing no DWI abnormalities and 84 with conditions like stroke and tumors. The 21,000 images were divided into 80% for training, 20% for validation, and 3500 for testing. FIELD STRENGTH/SEQUENCE: Seven MR scanners from four manufacturers with 1.5 T and 3 T magnetic field strengths. DWIs were acquired using spin-echo sequences and high-resolution T2WIs using the T2-SPACE sequence. ASSESSMENT: An experienced, board-certified radiologist evaluated the effectiveness of restoring high-resolution T2WI and harmonizing diverse DWI with metrics such as PSNR and SSIM, and the texture and frequency attributes were further analyzed using gray-level co-occurrence matrix and 1-dimensional power spectral density. The model's impact on machine-specific characteristics was gauged through the performance metrics of a ResNet-50 model. Comprehensive statistical tests were employed for statistical robustness, including McNemar's test and the Dice index. RESULTS: Our DL protocol reduced DWI contrast and resolution variation. ResNet-50 model's accuracy decreased from 0.9443 to 0.5786, precision from 0.9442 to 0.6494, recall from 0.9443 to 0.5786, and F1 score from 0.9438 to 0.5587. The t-SNE visualization indicated more consistent image features across multiple MR devices. Autoencoder halved learning iterations; Dice coefficient >0.74 confirmed signal reproducibility in 84 lesions. CONCLUSION: This study presents a DL strategy to mitigate batch effects in diffusion MR images, improving their quality and generalizability. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Multiple sclerosis plaques may undergo continuous myelin degradation: a cross-sectional study with myelin and axon-related quantitative magnetic resonance imaging metrics.

PURPOSE: We hypothesize that myelin is more susceptible to damage over time than axons. We investigated the association between the estimated duration from the onset of multiple sclerosis (MS) plaques and myelin- and axon-related quantitative synthetic magnetic resonance imaging (SyMRI) and neurite orientation dispersion and density imaging (NODDI) metrics. METHODS: We analyzed 31 patients with MS with 73 newly appeared plaques. Simple linear regression analysis was performed to assess the association between the estimated duration from the onset of plaques and quantitative MRI metrics. These metrics included the myelin volume fraction (MVF), axon volume fraction, and g-ratio in plaque and normal-appearing white matter. RESULTS: MS plaques with a longer estimated duration from onset were significantly correlated with a lower MVF (slope = - 0.0070, R2 = 0.0970), higher g-ratio (slope = 0.0078, R2 = 0.0842) (all P values < 0.05). CONCLUSION: These results suggested that myelin in plaques undergoes continuous damage, more so than axons. Myelin imaging with SyMRI and NODDI may be useful for the quantitative assessment of temporal changes in MS plaques.

3D quantitative synthetic MRI-derived cortical thickness and subcortical brain volumes: Scan-rescan repeatability and comparison with conventional T1 -weighted images.

BACKGROUND: Previous quantitative synthetic MRI of the brain has been solely performed in 2D. PURPOSE: To evaluate the feasibility of the recently developed sequence 3D-QALAS for brain cortical thickness and volumetric analysis. STUDY TYPE: Reproducibility/repeatability study. SUBJECTS: Twenty-one healthy volunteers (35.6 ± 13.8 years). FIELD STRENGTH/SEQUENCE: 3D T1 -weighted fast spoiled gradient recalled echo (FSPGR) sequence was performed once, and 3D-QALAS sequence was performed twice with a 3T scanner. ASSESSMENT: FreeSurfer and FIRST were used to measure cortical thickness and volume of subcortical structures, respectively. Agreement with FSPGR and scan-rescan repeatability were evaluated for 3D-QALAS. STATISTICAL TESTS: Percent relative difference and intraclass correlation coefficient (ICC) were used to assess reproducibility and scan-rescan repeatability of the 3D-QALAS sequence-derived measurements. RESULTS: Percent relative difference compared with FSPGR in cortical thickness of the whole cortex was 3.1%, and 89% of the regional areas showed less than 10% relative difference in cortical thickness. The mean ICC across all regions was 0.65, and 74% of the structures showed substantial to almost perfect agreement. For volumes of subcortical structures, the median percent relative differences were lower than 10% across all subcortical structures, except for the accumbens area, and all structures showed ICCs of substantial to almost perfect agreement. For the scan-rescan test, percent relative difference in cortical thickness of the whole cortex was 2.3%, and 97% of the regional areas showed less than 10% relative difference in cortical thickness. The mean ICC across all regions was 0.73, and 80% showed substantial to almost perfect agreement. For volumes of subcortical structures, relative differences were less than 10% across all subcortical structures except for the accumbens area, and all structures showed ICCs of substantial to almost perfect agreement. DATA CONCLUSION: 3D-QALAS could be reliably used for measuring cortical thickness and subcortical volumes in most brain regions. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1834-1842.

Aberrant myelination in patients with Sturge-Weber syndrome analyzed using synthetic quantitative magnetic resonance imaging.

PURPOSE: Accelerated myelination in the affected hemisphere has been demonstrated previously in patients with Sturge-Weber syndrome (SWS). This prospective study investigated myelin-related changes in patients with unilateral SWS using synthetic quantitative magnetic resonance imaging (qMRI). METHODS: Fourteen children with unilateral SWS were categorized according to age, i.e., ≤ 2 years (group A, n = 5, mean age 1.1 years, 3 males) and > 2 years (group B, n = 9, mean age 3.9 years, 4 males). All children underwent two-dimensional synthetic qMRI. The myelin volume in the cerebral hemisphere and white matter (WM) myelin volume fraction (MVF), proton density (PD), R1 and R2 relaxation rates ipsilateral to the leptomeningeal enhancement, and/or a port-wine birthmark were compared with the corresponding values in the contralateral hemisphere. RESULTS: In group A, 3 patients had a higher myelin volume in the ipsilateral hemisphere and a higher MVF, R1, and R2 and lower PD in the ipsilateral WM than on the contralateral side; the findings were the opposite in the remaining two patients. All patients in group B had a significantly lower myelin volume in the ipsilateral hemisphere (P < 0.05) and a lower MVF and R1 and higher PD in the ipsilateral WM than on the contralateral side (P < 0.0125). CONCLUSION: Higher estimated myelin was observed on the ipsilateral side in some patients aged ≤ 2 years and lower myelin on the ipsilateral side in all older patients. Synthetic qMRI might be useful for showing myelin-related abnormalities in SWS.

Brain tissue and myelin volumetric analysis in multiple sclerosis at 3T MRI with various in-plane resolutions using synthetic MRI.

PURPOSE: Synthetic MRI (SyMRI) enables automatic brain tissue and myelin volumetry based on the quantification of R1 and R2 relaxation rates and proton density. This study aimed to determine the validity of SyMRI brain tissue and myelin volumetry using various in-plane resolutions at 3T in patients with multiple sclerosis (MS). METHODS: We scanned 19 MS patients and 10 healthy age- and gender-matched controls using a 3T MR scanner with in-plane resolutions of 0.8, 1.8, and 3.6 mm. The acquisition times were 5 min 8 s, 2 min 52 s, and 2 min 1 s, respectively. White matter (WM), gray matter (GM), cerebrospinal fluid (CSF), and myelin and non-WM/GM/CSF (NoN) volumes; brain parenchymal volume (BPV); and intracranial volume (ICV) were compared between different in-plane resolutions. These parameters were also compared between both groups, after ICV normalization. RESULTS: No significant differences in measured volumes were noted between the 0.8 and 1.8 mm in-plane resolutions, except in NoN and CSF for healthy controls and NoN for MS patients. Meanwhile, significant volumetric differences were noted in most brain tissues when compared between the 3.6 and 0.8 or 1.8 mm resolution for both healthy controls and MS patients. The normalized WM volume, myelin volume, and BPV showed significant differences between controls and MS patients at in-plane resolutions of 0.8 and 1.8 mm. CONCLUSIONS: SyMRI brain tissue and myelin volumetry with in-plane resolution as low as 1.8 mm can be useful in the evaluation of MS with a short acquisition time of < 3 min.

White matter alterations in adult with autism spectrum disorder evaluated using diffusion kurtosis imaging.

PURPOSE: Autism spectrum disorder (ASD) is related to impairment in various white matter (WM) pathways. Utility of the recently developed two-compartment model of diffusion kurtosis imaging (DKI) to analyse axial diffusivity of WM is restricted by several limitations. The present study aims to validate the utility of model-free DKI in the evaluation of WM alterations in ASD and analyse the potential relationship between DKI-evident WM alterations and personality scales. METHODS: Overall, 15 participants with ASD and 15 neurotypical (NT) controls were scanned on a 3 T magnetic resonance (MR) scanner, and scores for autism quotient (AQ), systemising quotient (SQ) and empathising quotient (EQ) were obtained for both groups. Multishell diffusion-weighted MR data were acquired using two b-values (1000 and 2000 s/mm2). Differences in mean kurtosis (MK), radial kurtosis (RK) and axial kurtosis (AK) between the groups were evaluated using tract-based spatial statistics (TBSS). Finally, the relationships between the kurtosis indices and personality quotients were examined. RESULTS: The ASD group demonstrated significantly lower AK in the body and splenium of corpus callosum than the NT group; however, no other significant differences were identified. Negative correlations were found between AK and AQ or SQ, predominantly in WM areas related to social-emotional processing such as uncinate fasciculus, inferior fronto-occipital fasciculus, and inferior and superior longitudinal fasciculi. CONCLUSIONS: Model-free DKI and its indices may represent a novel, objective method for detecting the disease severity and WM alterations in patients with ASD.

Review of synthetic MRI in pediatric brains: Basic principle of MR quantification, its features, clinical applications, and limitations.

Quantitative magnetic resonance imaging (MRI) with multislice, multi-echo, and multi-delay acquisition enables simultaneous quantification of R1 and R2 relaxation rates, proton density, and the B1 field in a single acquisition, and requires only about 6 minutes for full-head coverage. Using dedicated SyMRI software, radiologists can generate any contrast-weighted image by manipulating the acquisition parameters, including repetition time, echo time, and inversion time. Moreover, automatic brain tissue segmentation, volumetry, and myelin measurement can also be performed. Using the SyMRI approach, a shorter scan time, an objective examination, and personalized MR imaging parameters can be obtained in daily clinical pediatric imaging. Here we summarize and review the use of SyMRI in imaging of the pediatric brain, including the basic principles of MR quantification along with its features, clinical applications, and limitations.

Reduced visualization of cerebral infarction on diffusion-weighted images with short diffusion times.

PURPOSE: Diffusion-weighted imaging (DWI) is a useful tool for early detection of cerebral infarction. However, recent reports have demonstrated that DWI with short effective diffusion time (∆eff) can obscure visualization of infarction. METHODS: We report three cases, including four acute-to-subacute infarctions, that demonstrated reduced visualization of the infarctions on DWI with shorter ∆eff. RESULTS: DWI was performed with different ∆eff: short and long ∆eff, using oscillating gradient spin-echo (OGSE) DWI, and intermediate ∆eff, using pulsed gradient spin-echo (PGSE) DWI. Different apparent diffusion coefficient values (due to different ∆eff) were also observed; these were considered to be the underlying causes of the under-evaluation of infarctions on DWI. CONCLUSION: The DWI with shorter ∆eff may obscure infarction. High-performance magnetic resonance imaging scanners with higher maximal gradient strength (Gmax) can perform DWI with shorter ∆eff than scanners with lower Gmax. Therefore, the appropriate ∆eff should be set for the detection of restricted diffusion.

Objective sleep of older primiparous Japanese women during the first 4 months postpartum: an actigraphic study.

This longitudinal study was designed to examine objective sleep parameters of older primiparous Japanese women during the first 4 months postpartum using actigraphy. The participants were 18 older primiparae (Mean (SD) = 37.06 (2.62) years, range 35-44 years) who gave birth to healthy neonates at one of three urban Japanese hospitals. Objective sleep quality was measured using actigraphy for 48 h at 1, 2 and 4 months postpartum. The Friedman test was used to test for differences in sleep parameters across time. Sleep duration (SMIN) increased significantly from 2 months (Mean (M) = 301.94 min) to 4 months (M = 372.78 min). Sleep efficiency (SE) increased significantly from 1 month (73.52%) to 2 (86.66%) and 4 months (89.05%). Waking after sleep onset (WASO) decreased significantly from 1 month (M = 114.64 min) to 2 (M = 40.18 min) and 4 months (M = 38.36 min) and long waking episodes (LWEP) significantly decreased from 1 month (4.67) to 2 (2.69) and 4 months (3.12). Persistent postpartum sleep problems can be a sign of postpartum depression as well as health problems among infants.

Comparing older and younger Japanese primiparae: fatigue, depression and biomarkers of stress.

This cohort study of primiparae was conducted to answer the following questions: Do older (≧ 35 years) and younger (20-29 years) Japanese primiparous mothers differ when comparing biomarkers of stress and measures of fatigue and depression? Are there changes in fatigue, depression and stress biomarkers when comparing older and younger mothers during the postpartum period? The Postnatal Accumulated Fatigue Scale and the Edinburgh Postnatal Depression Scale were administered in a time-series method four times: shortly after birth and monthly afterwards. Assays to measure biomarkers of stress, urinary 17-ketosteroids, urinary 17-hydroxycorticosteroids and salivary chromogranin-A, were collected shortly after delivery and at 1 month postpartum in both groups and a third time in older mothers at the 4th month. Statistical testing showed very little difference in fatigue, depression or stress biomarkers between older and younger mothers shortly after birth or 1 month later. Accumulated fatigue and depression scores of older mothers were highest 1 month after delivery. Additional cohort studies are required to characterize physical/psychological well-being of older Japanese primiparae.

Fragmented sleep and fatigue during postpartum hospitalization in older primiparous women.

The objective of this cross-sectional study was to investigate the associations among sleep characteristics, feeding variables, and fatigue among older Japanese primiparas (≥ 35 years old) during hospitalization after childbirth. A convenience sample of 16 participants who had given birth to a single newborn were recruited from maternity wards, and before discharge they completed a sleep assessment and questionnaires. Sleep characteristics were assessed using actigraphs. Diaries of daily activities recorded infant caregiving and subjective hours of sleep. The degree of fatigue was assessed using self-administered questionnaires. Although participants' sleep was found to be significantly fragmented by the average number of feeds per night, sleep loss in this sample was not severe compared with previous actigraph studies of young Japanese mothers. Lower percentages of sleep efficiency (percentage of sleep between going to bed and waking up) and parameters of fragmented sleep were significantly correlated with higher degrees of fatigue. Nurses and other healthcare providers should observe mothers' sleep and assess levels of fatigue. Assistance should be offered to mothers who are tired, so that they can have less fragmented sleep during the night.

Postpartum experiences of older Japanese primiparas during the first month after childbirth.

This study aimed to describe the postpartum experiences of older Japanese primiparas during the first month after childbirth. The participants were 21 primiparous women over 35 years of age who gave birth to a healthy child at three urban hospitals. Data were collected from July 2011 to April 2012 through a semi-structured interview about postpartum experiences after discharge. Data were analysed using content analysis. We obtained Institutional Review Boards' approval and written informed consent from all participants prior to study initiation. Thirteen themes of postpartum experiences were extracted. The findings revealed that the mothers' experiences varied greatly and were highly personal. Also, participants described common experiences, unique child-care support needs and the strengths of older primiparas. Understanding the postpartum experiences of older primiparas assists health-care professionals to identify better ways to provide appropriate support.

Older Japanese primiparas' experiences at the time of their post-delivery hospital stay.

The purpose of this study was to gain a deeper understanding of the postpartum experiences of older primiparas at the time of their postpartum hospital stay. Participants were Japanese primiparas aged 35-44 years who gave birth, without abnormalities for either the mother or child. Data were obtained using a semi-structured interview with 22 participants. Thirteen themes emerged through content analysis. We found that there were distinctive experiences, which included 'the health and growth of the baby: relief and continued anxiety', 'awareness of strengths and of concerns of primiparas', 'meaning of the pregnancy and childbirth experience' and 'developing one's own child-care approach'. Findings suggest that nursing care during the post-delivery hospital stay should use the unique strengths of older primiparas to enable their smooth transition to maternal role attainment.

Overexpression of cathepsin D in malignant melanoma.

Cathepsin D is an aspartic lysosomal endopeptidase present in most mammalian cells. Overexpression of cathepsin D is associated with the progression of several human cancers including melanoma. We examined the expression levels of cathepsin D in 20 primary malignant melanomas, 20 metastatic malignant melanomas, 20 benign nevus pigmentosus and 10 normal skin samples in Japanese. In normal skin, granular or dotted pattern of positive staining was observed along the granular layer of epidermis and hair follicle with apparent moderate to strong staining in sebaceous and eccrine glands. The percent positivity and staining intensity of cathepsin D in primary and metastatic malignant melanomas were significantly higher than that of nevus pigmentosus. Moreover, the expression levels of cathepsin D in metastatic malignant melanomas were significantly higher than those of primary malignant melanomas. Data from our and previous reports strongly supports a notion that the upregulation of cathepsin D may be critically involved in the malignant transformation and progression of melanocytic tumors.

Investigation of time-dependent diffusion in extra-axial brain tumors using oscillating-gradient spin-echo.

Oscillating gradient spin-echo (OGSE) sequences provide access to short diffusion times and may provide insight into micro-scale internal structures of pathologic lesions based on an analysis of changes in diffusivity with differing diffusion times. We hypothesized that changes in diffusivity acquired with a shorter diffusion time may permit elucidation of properties related to the internal structure of extra-axial brain tumors. This study aimed to investigate the utility of changes in diffusivity between short and long diffusion times for characterizing extra-axial brain tumors. In total, 12 patients with meningothelial meningiomas, 13 patients with acoustic neuromas, and 11 patients with pituitary adenomas were scanned with a 3 T magnetic resonance imaging (MRI) scanner with diffusion-weighted imaging (DWI) using OGSE and pulsed gradient spin-echo (PGSE) (effective diffusion times [Δeff]: 6.5 ms and 35.2 ms) with b-values of 0 and 1000 s/mm2. Relative percentage changes between shorter and longer diffusion times were calculated using region-of-interest (ROI) analysis of brain tumors on λ1, λ2, λ3, and mean diffusivity (MD) maps. The diffusivities of PGSE, OGSE, and relative percentage changes were compared among each tumor type using a multiple comparisons Steel-Dwass test. The mean (standard deviation) MD at Δeff of 6.5 ms was 1.07 ± 0.23 10-3 mm2/s, 1.19 ± 0.18 10-3 mm2/s, 1.19 ± 0.21 10-3 mm2/s for meningothelial meningiomas, acoustic neuromas, and pituitary adenomas, respectively. The mean (standard deviation) MD at Δeff of 35.2 ms was 0.93 ± 0.22 10-3 mm2/s, 1.07 ± 0.19 10-3 mm2/s, 0.82 ± 0.21 10-3 mm2/s for meningothelial meningiomas, acoustic neuromas, and pituitary adenomas, respectively. The mean (standard deviation) of the relative percentage change was 15.7 ± 4.4%, 12.4 ± 8.2%, 46.8 ± 11.3% for meningothelial meningiomas, acoustic neuromas, and pituitary adenomas, respectively. Compared to meningiomas and acoustic neuromas, pituitary adenoma exhibited stronger diffusion time-dependence with diffusion times between 6.5 ms and 35.2 ms (P < 0.05). In conclusion, differences in diffusion time-dependence may be attributed to differences in the internal structures of brain tumors. DWI with a short diffusion time may provide additional information on the microstructure of each tumor and contribute to tumor diagnosis.

Glymphatic System Dysfunction in Myelin Oligodendrocyte Glycoprotein Immunoglobulin G Antibody-Associated Disorders: Association with Clinical Disability.

BACKGROUND AND PURPOSE: Impaired glymphatic function has been suggested to be implicated in the pathophysiology of MS and aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder. This study aimed to investigate the interstitial fluid dynamics in the brain in patients with myelin oligodendrocyte glycoprotein antibody disorders (MOGAD), another demyelinating disorder, using a noninvasive imaging technique called the diffusivity along the perivascular space (ALPS) index. MATERIALS AND METHODS: A prospective study was conducted on 16 patients with MOGAD in remission and 22 age- and sex-matched healthy control subjects. MR imaging was performed using a 3T scanner, and the ALPS index was calculated using diffusion MR imaging data with a b-value of 1000 s/mm2. The ALPS index and gray matter volumes were compared between the 2 groups, and these parameters were correlated with the Expanded Disability Status Scale. RESULTS: The mean ALPS index of patients with MOGAD was significantly lower than that of healthy controls (Cohen d = 0.93, false discovery rate-corrected P = .02). The lower mean ALPS index was significantly associated with a worse Expanded Disability Status Scale score (Spearman ρ = -0.51; 95% CI, -0.85 to -0.02; P = .03). However, cortical volume and deep gray matter volume were not significantly different between the 2 groups, and they were not correlated with the Expanded Disability Status Scale. CONCLUSIONS: This study suggests that patients with MOGAD may have impaired glymphatic function, as measured by the ALPS index, which is associated with patient disability. Further study is warranted with a larger sample size.

Evaluation of the training course for a nursing intervention programme to promote maternal role attainment in pregnant Japanese women who have undergone assisted reproductive technology.

This study evaluated the effectiveness of a 2 day training course for a nursing intervention programme to promote maternal role attainment in pregnant Japanese women who have undergone assisted reproductive technology. Participants were 12 Japanese nurses with more than 3 years of clinical experience at reproductive institutions. The effectiveness of the training course was evaluated by assessing the following: (i) understanding of the nursing intervention programme; (ii) attitudes of nurses towards women who are pregnant following assisted reproductive technology; and (iii) self-efficacy for implementing the programme. The training course was effective in increasing basic understanding of the programme and in assisting self-evaluation of the attitudes of participants towards pregnant women. However, acquisition of effective interview skills and changes to make the programme clinically feasible are still needed. Findings suggest that researchers who use this training programme may need to evaluate and include training of nurses in interview skills suitable for their working environments.

Time-dependent Diffusion in Brain Abscesses Investigated with Oscillating-gradient Spin-echo.

Oscillating-gradient spin-echo sequences enable the measurement of diffusion weighting with a short diffusion time and can provide indications of internal structures. We report two cases of brain abscess in which the apparent diffusion coefficient (ADC) values appear higher at short diffusion times in comparison with those at long diffusion times. Diffusion time dependence of the ADC in brain abscesses suggests not only substrate viscosity but also restricted diffusion due to the structure within the lesions.

Advanced Diffusion MR Imaging for Multiple Sclerosis in the Brain and Spinal Cord.

Diffusion tensor imaging (DTI) has been established its usefulness in evaluating normal-appearing white matter (NAWM) and other lesions that are difficult to evaluate with routine clinical MRI in the evaluation of the brain and spinal cord lesions in multiple sclerosis (MS), a demyelinating disease. With the recent advances in the software and hardware of MRI systems, increasingly complex and sophisticated MRI and analysis methods, such as q-space imaging, diffusional kurtosis imaging, neurite orientation dispersion and density imaging, white matter tract integrity, and multiple diffusion encoding, referred to as advanced diffusion MRI, have been proposed. These are capable of capturing in vivo microstructural changes in the brain and spinal cord in normal and pathological states in greater detail than DTI.This paper reviews the current status of recent advanced diffusion MRI for assessing MS in vivo as part of an issue celebrating two decades of magnetic resonance in medical sciences (MRMS), an official journal of the Japanese Society of Magnetic Resonance in Medicine.

Time-dependent Diffusion in Transient Splenial Lesion: Comparison between Oscillating-gradient Spin-echo Measurements and Monte-Carlo Simulation.

The microstructural underpinnings of reduced diffusivity in transient splenial lesion remain unclear. Here, we report findings from oscillating gradient spin-echo (OGSE) diffusion imaging in a case of transient splenial lesion. Compared with normal-appearing white matter, the splenial lesion exhibited greater differences between diffusion time t = 6.5 and 35.2 ms, indicating microstructural changes occurring within the corresponding length scale. We also conducted 2D Monte-Carlo simulation. The results suggested that emergence of small and non-exchanging compartment, as often imagined in intramyelinic edema, does not fit well with the in vivo observation. Simulations with axonal swelling and microglial infiltration yielded results closer to the in vivo observations. The present report exemplifies the importance of controlling t for more specific radiological image interpretations.