Noninvasive Magnetic Resonance Imaging Measures of Glymphatic System Activity.

The comprehension of the glymphatic system, a postulated mechanism responsible for the removal of interstitial solutes within the central nervous system (CNS), has witnessed substantial progress recently. While direct measurement techniques involving fluorescence and contrast agent tracers have demonstrated success in animal studies, their application in humans is invasive and presents challenges. Hence, exploring alternative noninvasive approaches that enable glymphatic research in humans is imperative. This review primarily focuses on several noninvasive magnetic resonance imaging (MRI) techniques, encompassing perivascular space (PVS) imaging, diffusion tensor image analysis along the PVS, arterial spin labeling, chemical exchange saturation transfer, and intravoxel incoherent motion. These methodologies provide valuable insights into the dynamics of interstitial fluid, water permeability across the blood-brain barrier, and cerebrospinal fluid flow within the cerebral parenchyma. Furthermore, the review elucidates the underlying concept and clinical applications of these noninvasive MRI techniques, highlighting their strengths and limitations. It addresses concerns about the relationship between glymphatic system activity and pathological alterations, emphasizing the necessity for further studies to establish correlations between noninvasive MRI measurements and pathological findings. Additionally, the challenges associated with conducting multisite studies, such as variability in MRI systems and acquisition parameters, are addressed, with a suggestion for the use of harmonization methods, such as the combined association test (COMBAT), to enhance standardization and statistical power. Current research gaps and future directions in noninvasive MRI techniques for assessing the glymphatic system are discussed, emphasizing the need for larger sample sizes, harmonization studies, and combined approaches. In conclusion, this review provides invaluable insights into the application of noninvasive MRI methods for monitoring glymphatic system activity in the CNS. It highlights their potential in advancing our understanding of the glymphatic system, facilitating clinical applications, and paving the way for future research endeavors in this field. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

Accelerated Two-Point Dixon MR Angiography Improves Diagnostic Performance for Cervical Artery Diseases.

BACKGROUND: Nonenhanced MR angiography (MRA) studies are often used to manage acute and chronic large cervical artery disease, but lengthy scan times limit their clinical usefulness. PURPOSE: To develop an accelerated cervical MRA and test its diagnostic performance. STUDY TYPE: Prospective. POPULATION: Patients with cervical artery disease (n = 32, 17 males). FIELD STRENGTH/SEQUENCE: 3.0 T; accelerated two-point Dixon three-dimensional Cartesian spoiled gradient-echo (FLEXA) and conventional time-of-flight MRA (cMRA) sequences. ASSESSMENT: All patients underwent FLEXA (1'28″) and cMRA (6'47″) acquisitions. Quantitative evaluation (artery-to-background signal ratio and a blur metric) and qualitative evaluation using diagnostic performance measured by the sensitivity, specificity, and positive/negative predictive values (PPV/NPV), and vessel and plaque visualization scores from three board-certified radiologists' (with 10, 11, and 12 years of experience) independent readings using maximum intensity projection (MIP) for luminal diseases and axial images for plaque. The reference standards were contrast-enhanced angiography and fat-saturated T1-weighted images, respectively. STATISTICAL TESTS: All measures were compared between FLEXA and cMRA using the paired t, Wilcoxon signed-rank, McNemar's, or chi-squared test, as appropriate. Interreader agreement was assessed using Cohen's κ. P < 0.05 was considered statistically significant. RESULTS: The artery-to-background signal ratio was significantly higher for FLEXA (FLEXA: 7.20 ± 1.63 [fat]; 4.26 ± 0.52 [muscle]; cMRA: 2.57 ± 0.49 [fat]), while image blurring was significantly less (FLEXA: 0.24 ± 0.016; cMRA: 0.30 ± 0.029). In luminal disease detection, sensitivity (FLEXA: 0.97/0.91/0.91; cMRA:0.71/0.69/0.63), specificity (FLEXA: 0.98/0.93/0.98; cMRA:0.93/0.85/0.92), PPV (FLEXA: 0.92/0.86/0.86; cMRA: 0.64/0.5/0.58), and NPV (FLEXA: 0.99/0.98/0.98; cMRA: 0.92/0.91/0.9) were significantly higher for FLEXA. interreader agreement was substantial to almost perfect for FLEXA (κ = 0.82/0.86/0.78) and moderate to substantial for cMRA (κ = 0.67/0.56/0.57). MIP visualization scores were significantly higher for FLEXA, with substantial to almost perfect interreader agreement (FLEXA: κ = 0.83/0.86/0.82; cMRA: κ = 0.89/0.79/0.79). In plaque detection, sensitivity (FLEXA: 0.9/0.9/0.7; cMRA: 0.3/0.6/0.2) and specificity (FLEXA: 1/0.87/1; cMRA: 0.93/0.63/0.97) were significantly higher for FLEXA in two of three readers. The interreader plaque detection agreement was fair to substantial (FLEXA: κ = 0.63/0.69/0.48; cMRA: κ = 0.21/0.45/0.20). Side-by-side plaque and vessel wall visualization was superior for FLEXA in all readers, with moderate to substantial interreader agreement (plaque: κ = 0.73/0.73/0.77; vessel wall: κ = 0.57/0.40/0.39). DATA CONCLUSION: FLEXA enhanced visualization of the cervical arterial system and improved diagnostic performance for luminal abnormalities and plaques in patients with cervical artery diseases. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Cross-scanner reproducibility and harmonization of a diffusion MRI structural brain network: A traveling subject study of multi-b acquisition.

Characterization of brain networks by diffusion MRI (dMRI) has rapidly evolved, and there are ongoing movements toward data sharing and multi-center studies. To extract meaningful information from multi-center data, methods to correct for the bias caused by scanner differences, that is, harmonization, are urgently needed. In this work, we report the cross-scanner differences in structural network analyses using data from nine traveling subjects (four males and five females, 21-49 years-old) who underwent scanning using four 3T scanners (public database available from the Brain/MINDS Beyond Human Brain MRI project (http://mriportal.umin.jp/)). The reliability and reproducibility were compared to those of data from another set of four subjects (all males, 29-42 years-old) who underwent scan-rescan (interval, 105-147 days) with the same scanner as well as scan-rescan data from the Human Connectome Project database. The results demonstrated that the reliability of the edge weights and graph theory metrics was lower for data including different scanners, compared to the scan-rescan with the same scanner. Besides, systematic differences between scanners were observed, indicating the risk of bias in comparing networks obtained from different scanners directly. We further demonstrate that it is feasible to reduce inter-scanner variabilities while preserving the inter-subject differences among healthy individuals by modeling the scanner effects at the level of network matrices, when traveling-subject data are available for calibration between scanners. The present data and results are expected to serve as a basis for developing and evaluating novel harmonization methods.

Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability.

Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P < 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P < 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P < 0.0001), brainstem (r = 0.45, P < 0.0001) and spinal cord (r = 0.57, P < 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.

Structural connectivity changes in the cerebral pain matrix in burning mouth syndrome: a multi-shell, multi-tissue-constrained spherical deconvolution model analysis.

PURPOSE: Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome. Previous studies have attempted to determine the brain connectivity features in BMS using functional and structural magnetic resonance imaging. However, no study has investigated the structural connectivity using multi-shell, multi-tissue-constrained spherical deconvolution (MSMT-CSD), anatomically constrained tractography (ACT), and spherical deconvolution informed filtering of tractograms (SIFT). Therefore, this study aimed to assess the differences in brain structural connectivity of patients with BMS and healthy controls using probabilistic tractography with these methods, and graph analysis. METHODS: Fourteen patients with BMS and 11 age- and sex-matched healthy volunteers underwent 3-T magnetic resonance imaging. MSMT-CSD-based probabilistic structural connectivity was computed using the second-order integration over fiber orientation distributions algorithm based on nodes set in 84 anatomical cortical regions with ACT and SIFT. A t-test was performed for comparisons between the BMS and healthy control brain networks. RESULTS: The betweenness centrality was significantly higher in the left insula, right amygdala, and right lateral orbitofrontal cortex and significantly lower in the right inferotemporal cortex in the BMS group than that in healthy controls. However, no significant difference was found in the clustering coefficient, node degree, and small-worldness between the two groups. CONCLUSION: Graph analysis of brain probabilistic structural connectivity, based on diffusion imaging using an MSMT-CSD model with ACT and SIFT, revealed alterations in the regions comprising the pain matrix and medial pain ascending pathway. These results highlight the emotional-affective profile of BMS, which is a type of chronic pain syndrome.

Spatial distribution of multiple sclerosis lesions in the cervical spinal cord.

Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T2- and T2*-weighted axial and sagittal MRI scans acquired at 3 or 7 T. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P < 0.001), which was further confirmed by absolute and normalized lesion volumes (P < 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P < 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P < 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P < 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups.

Accelerated acquisition of carotid MR angiography using 3D gradient-echo imaging with two-point Dixon.

This pilot study tests the feasibility of rapid carotid MR angiography using the liver acquisition with volume acceleration-flex technique (LAVA MRA). Seven healthy volunteers and 21 consecutive patients suspected of carotid stenosis underwent LAVA and conventional time-of-flight (cTOF) MRAs. Artery-to-fat and artery-to-muscle signal intensity ratios were manually measured. LAVA MRA exhibited a significantly larger artery-to-fat signal intensity ratio compared with cTOF MRA in all slices (P < 0.001) and exhibited a larger (P < 0.001) or equivalent (P = 1.0) artery-to-muscle signal intensity ratio in the extracranial carotid arteries. The image quality of the cervical carotid bifurcation and the signal change on each MRA were visually assessed and compared among the MRAs. There was no significant difference between the two MRAs in visual assessment. LAVA MRA can provide visualization similar to cTOF MRA in the evaluation of the cervical carotid bifurcation while reducing scan time by one-fifth.

Scan-rescan and inter-vendor reproducibility of neurite orientation dispersion and density imaging metrics.

PURPOSE: The reproducibility of neurite orientation dispersion and density imaging (NODDI) metrics in the human brain has not been explored across different magnetic resonance (MR) scanners from different vendors. This study aimed to evaluate the scan-rescan and inter-vendor reproducibility of NODDI metrics in white and gray matter of healthy subjects using two 3-T MR scanners from two vendors. METHODS: Ten healthy subjects (7 males; mean age 30 ± 7 years, range 23-37 years) were included in the study. Whole-brain diffusion-weighted imaging was performed with b-values of 1000 and 2000 s/mm2 using two 3-T MR scanners from two different vendors. Automatic extraction of the region of interest was performed to obtain NODDI metrics for whole and localized areas of white and gray matter. The coefficient of variation (CoV) and intraclass correlation coefficient (ICC) were calculated to assess the scan-rescan and inter-vendor reproducibilities of NODDI metrics. RESULTS: The scan-rescan and inter-vendor reproducibility of NODDI metrics (intracellular volume fraction and orientation dispersion index) were comparable with those of diffusion tensor imaging (DTI) metrics. However, the inter-vendor reproducibilities of NODDI (CoV = 2.3-14%) were lower than the scan-rescan reproducibility (CoV: scanner A = 0.8-3.8%; scanner B = 0.8-2.6%). Compared with the finding of DTI metrics, the reproducibility of NODDI metrics was lower in white matter and higher in gray matter. CONCLUSION: The lower inter-vendor reproducibility of NODDI in some brain regions indicates that data acquired from different MRI scanners should be carefully interpreted.

Evaluation of white matter microstructure in patients with Parkinson's disease using microscopic fractional anisotropy.

PURPOSE: Micro fractional anisotropy (µFA) is more accurate than conventional fractional anisotropy (FA) for assessing microscopic tissue properties and can overcome limitations related to crossing white matter fibres. We compared µFA and FA for evaluating white matter changes in patients with Parkinson's disease (PD). METHODS: We compared FA and µFA measures between 25 patients with PD and 25 age- and gender-matched healthy controls using tract-based spatial statistics (TBSS) analysis. We also examined potential correlations between changes, revealed by conventional FA or µFA, and disease duration or Unified Parkinson's Disease Rating Scale (UPDRS)-III scores. RESULTS: Compared with healthy controls, patients with PD had significantly reduced µFA values, mainly in the anterior corona radiata (ACR). In the PD group, µFA values (primarily those from the ACR) were significantly negatively correlated with UPDRS-III motor scores. No significant changes or correlations with disease duration or UPDRS-III scores with tissue properties were detected using conventional FA. CONCLUSION: µFA can evaluate microstructural changes that occur during white matter degeneration in patients with PD and may overcome a key limitation of FA.

Automatic segmentation of the spinal cord and intramedullary multiple sclerosis lesions with convolutional neural networks.

The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in MS. Automating this operation eliminates inter-rater variability and increases the efficiency of large-throughput analysis pipelines. Robust and reliable segmentation across multi-site spinal cord data is challenging because of the large variability related to acquisition parameters and image artifacts. In particular, a precise delineation of lesions is hindered by a broad heterogeneity of lesion contrast, size, location, and shape. The goal of this study was to develop a fully-automatic framework - robust to variability in both image parameters and clinical condition - for segmentation of the spinal cord and intramedullary MS lesions from conventional MRI data of MS and non-MS cases. Scans of 1042 subjects (459 healthy controls, 471 MS patients, and 112 with other spinal pathologies) were included in this multi-site study (n = 30). Data spanned three contrasts (T1-, T2-, and T2∗-weighted) for a total of 1943 vol and featured large heterogeneity in terms of resolution, orientation, coverage, and clinical conditions. The proposed cord and lesion automatic segmentation approach is based on a sequence of two Convolutional Neural Networks (CNNs). To deal with the very small proportion of spinal cord and/or lesion voxels compared to the rest of the volume, a first CNN with 2D dilated convolutions detects the spinal cord centerline, followed by a second CNN with 3D convolutions that segments the spinal cord and/or lesions. CNNs were trained independently with the Dice loss. When compared against manual segmentation, our CNN-based approach showed a median Dice of 95% vs. 88% for PropSeg (p ≤ 0.05), a state-of-the-art spinal cord segmentation method. Regarding lesion segmentation on MS data, our framework provided a Dice of 60%, a relative volume difference of -15%, and a lesion-wise detection sensitivity and precision of 83% and 77%, respectively. In this study, we introduce a robust method to segment the spinal cord and intramedullary MS lesions on a variety of MRI contrasts. The proposed framework is open-source and readily available in the Spinal Cord Toolbox.

Diffusional kurtosis imaging and white matter microstructure modeling in a clinical study of major depressive disorder.

Major depressive disorder (MDD) is a globally prevalent psychiatric disorder that results from disruption of multiple neural circuits involved in emotional regulation. Although previous studies using diffusion tensor imaging (DTI) found smaller values of fractional anisotropy (FA) in the white matter, predominantly in the frontal lobe, of patients with MDD, studies using diffusion kurtosis imaging (DKI) are scarce. Here, we used DKI whole-brain analysis with tract-based spatial statistics (TBSS) to investigate the brain microstructural abnormalities in MDD. Twenty-six patients with MDD and 42 age- and sex-matched control subjects were enrolled. To investigate the microstructural pathology underlying the observations in DKI, a compartment model analysis was conducted focusing on the corpus callosum. In TBSS, the patients with MDD showed significantly smaller values of FA in the genu and frontal portion of the body of the corpus callosum. The patients also had smaller values of mean kurtosis (MK) and radial kurtosis (RK), but MK and RK abnormalities were distributed more widely compared with FA, predominantly in the frontal lobe but also in the parietal, occipital, and temporal lobes. Within the callosum, the regions with smaller MK and RK were located more posteriorly than the region with smaller FA. Model analysis suggested significantly smaller values of intra-neurite signal fraction in the body of the callosum and greater fiber dispersion in the genu, which were compatible with the existing literature of white matter pathology in MDD. Our results show that DKI is capable of demonstrating microstructural alterations in the brains of patients with MDD that cannot be fully depicted by conventional DTI. Though the issues of model validation and parameter estimation still remain, it is suggested that diffusion MRI combined with a biophysical model is a promising approach for investigation of the pathophysiology of MDD.

Prospective estimation of mean axon diameter and extra-axonal space of the posterior limb of the internal capsule in patients with idiopathic normal pressure hydrocephalus before and after a lumboperitoneal shunt by using q-space diffusion MRI.

OBJECTIVES: To prospectively estimate the mean axon diameter (MAD) and extracellular space of the posterior limb of the internal capsule (PLIC) in patients with idiopathic normal pressure hydrocephalus (iNPH) before and after a lumboperitoneal (LP) shunting operation using q-space diffusion MRI analysis. METHODS: We studied 12 consecutive patients with iNPH and 12 controls at our institution. After conventional magnetic resonance imaging (MRI), q-space image (QSI) data were acquired with a 3-T MRI scanner. The MAD and extra-axonal space of the PLIC before and after LP shunting were calculated using two-component q-space imaging analyses; the before and after values were compared. RESULTS: After LP shunt surgery, the extracellular space of the PLIC was significantly higher than that of the same patients before the operation (one-way analysis of variance (ANOVA) with Scheffé's post-hoc test, P = 0.024). No significant differences were observed in the PLIC axon diameters among normal controls or in patients before and after surgery. CONCLUSION: Increases in the root mean square displacement in the extra-axonal space of the PLIC in patients with iNPH after an LP shunt procedure are associated with the microstructural changes of white matter and subsequent abatement of patient symptoms. KEY POINTS: • Q-space diffusion MRI provides information on microstructural changes in the corticospinal tract • Lumboperitoneal (LP) shunting operation is useful for idiopathic normal pressure hydrocephalus • Q-space measurement may be a biomarker for the effect of the LP shunt procedure.

Neurite orientation dispersion and density imaging in the substantia nigra in idiopathic Parkinson disease.

OBJECTIVES: We used neurite orientation dispersion and density imaging (NODDI) to quantify changes in the substantia nigra pars compacta (SNpc) and striatum in Parkinson disease (PD). METHODS: Diffusion-weighted magnetic resonance images were acquired from 58 PD patients and 36 age- and sex-matched controls. The intracellular volume fraction (Vic), orientation dispersion index (OD), and isotropic volume fraction (Viso) of the basal ganglia were compared between groups. Multivariate logistic regression analysis determined which diffusion parameters were independent predictors of PD. Receiver operating characteristic (ROC) analysis compared the diagnostic accuracies of the evaluated indices. Pearson coefficient analysis correlated each diffusional parameter with disease severity. RESULTS: Vic in the contralateral SNpc and putamen were significantly lower in PD patients than in healthy controls (P < 0.00058). Vic and OD in the SNpc and putamen showed significant negative correlations (P < 0.05) with disease severity. Multivariate logistic analysis revealed that Vic (P = 0.0000046) and mean diffusivity (P = 0.019) in the contralateral SNpc were the independent predictors of PD. In the ROC analysis, Vic in the contralateral SNpc showed the best diagnostic performance (mean cutoff, 0.62; sensitivity, 0.88; specificity, 0.83). CONCLUSION: NODDI is likely to be useful for diagnosing PD and assessing its progression. KEY POINTS: • Neurite orientation dispersion and density imaging (NODDI) is a new diffusion MRI technique • NODDI estimates neurite microstructure more specifically than diffusion tensor imaging • By using NODDI, nigrostriatal alterations in PD can be evaluated in vivo • NOODI is useful for diagnosing PD and assessing its disease progression.

Analysis of normal-appearing white matter of multiple sclerosis by tensor-based two-compartment model of water diffusion.

OBJECTIVES: To compare the significance of the two-compartment model, considering diffusional anisotropy with conventional diffusion analyzing methods regarding the detection of occult changes in normal-appearing white matter (NAWM) of multiple sclerosis (MS). METHODS: Diffusion-weighted images (nine b-values with six directions) were acquired from 12 healthy female volunteers (22-52 years old, median 33 years) and 13 female MS patients (24-48 years old, median 37 years). Diffusion parameters based on the two-compartment model of water diffusion considering diffusional anisotropy was calculated by a proposed method. Other parameters including diffusion tensor imaging and conventional apparent diffusion coefficient (ADC) were also obtained. They were compared statistically between the control and MS groups. RESULTS: Diffusion of the slow diffusion compartment in the radial direction of neuron fibers was elevated in MS patients (0.121 × 10(-3) mm2/s) in comparison to control (0.100 × 10(-3) mm(2)/s), the difference being significant (P = 0.001). The difference between the groups was not significant in other comparisons, including conventional ADC and fractional anisotropy (FA) of diffusion tensor imaging. CONCLUSION: The proposed method was applicable to clinically acceptable small data. The parameters obtained by this method improved the detectability of occult changes in NAWM compared to the conventional methods. KEY POINTS: • Water diffusion was compared between the controls and multiple sclerosis patients. • A two-compartment model, considering diffusional anisotropy was selected for water diffusion analysis. • Axial and radial diffusion of fast and slow diffusion components were evaluated. • A new method was developed to obtain the metrics stably. • The metrics indicated high detectability of slight differences between the groups.

A preliminary diffusional kurtosis imaging study of Parkinson disease: comparison with conventional diffusion tensor imaging.

INTRODUCTION: Diffusional kurtosis imaging (DKI) is a more sensitive technique than conventional diffusion tensor imaging (DTI) for assessing tissue microstructure. In particular, it quantifies the microstructural integrity of white matter, even in the presence of crossing fibers. The aim of this preliminary study was to compare how DKI and DTI show white matter alterations in Parkinson disease (PD). METHODS: DKI scans were obtained with a 3-T magnetic resonance imager from 12 patients with PD and 10 healthy controls matched by age and sex. Tract-based spatial statistics were used to compare the mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA) maps of the PD patient group and the control group. In addition, a region-of-interest analysis was performed for the area of the posterior corona radiata and superior longitudinal fasciculus (SLF) fiber crossing. RESULTS: FA values in the frontal white matter were significantly lower in PD patients than in healthy controls. Reductions in MK occurred more extensively throughout the brain: in addition to frontal white matter, MK was lower in the parietal, occipital, and right temporal white matter. The MK value of the area of the posterior corona radiata and SLF fiber crossing was also lower in the PD group. CONCLUSION: DKI detects changes in the cerebral white matter of PD patients more sensitively than conventional DTI. In addition, DKI is useful for evaluating crossing fibers. By providing a sensitive index of brain pathology in PD, DKI may enable improved monitoring of disease progression.

Accelerated myelination along fiber tracts in patients with hemimegalencephaly.

BACKGROUND AND PURPOSE: In infants with hemimegalencephaly, asymmetrical white-matter intensities suggestive of advanced myelination are observed as well as aberrant midsagittal fibers (AMFs) specific to hemimegalencephaly. Also noted are otherwise unreported abnormally enlarged periventricular fibers (APVFs) running anteroposteriorly along the caudate nucleus. This study investigated the degree of myelination and presence of aberrant fibers in hemimegalencephaly through a retrospective review of MRI scans in relation to histopathological findings. MATERIALS AND METHODS: MRI scans of 24 infants with hemimegalencephaly (13 boys and 11 girls, 1-9 months old) were evaluated, focusing on the presence and signal intensities of AMFs and APVFs. White-matter signal intensities on T1- and T2-weighted imaging of the cerebral hemisphere were also evaluated and compared with the timetable for normal myelination. Surgical specimens were pathologically examined with Klüver-Barrera staining in four patients. RESULTS: AMFs and APVFs were observed in 18 and nine patients, respectively, while 22 patients had accelerated myelination of the megalencephalic hemisphere that tended to extend along fiber pathways including AMFs and APVFs. In six cases, accelerated myelination even extended into the contralateral hemisphere via the corpus callosum or AMFs. Histopathological analysis identified hypermyelination with disarrayed myelinated fibers corresponding to MRI findings. CONCLUSION: Accelerated myelination is frequently observed in patients with hemimegalencephaly and tends to extend along fiber pathways, including aberrant or abnormal fibers, as seen in 75% of hemimegalencephaly patients. Accelerated myelination may reflect propagation pathways of abnormal brain activity in such patients.

Prognostic value of post-treatment (18)F-FDG PET/CT for advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy.

OBJECTIVE: To clarify the prognostic value of post-treatment (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with advanced head and neck squamous cell carcinoma (HNSCC) after combined intra-arterial chemotherapy and radiotherapy (IACR). METHODS: Thirty-six patients with HNSCC who underwent IACR were recruited. The period from the end of IACR to the last post-treatment (18)F-FDG PET/CT examination was 8-12 weeks. Both patient-based and lesion-based analyses were used to evaluate the PET/CT images. For lesion-based analysis, 36 regions (12 lesions of recurrences and 24 scars at primary sites) were selected. The Kaplan-Meier method was used to assess the overall survival (OS) stratified by (18)F-FDG uptake or visual interpretation results. RESULTS: Twelve patients with recurrence were identified by six months after IACR. The sensitivity and specificity in the patient-based analysis were 67% (8/12) and 88% (21/24), respectively. The mean OS was estimated to be 12.1 months (95% CI, 6.3-18.0 months) for the higher maximum standardized uptake value (SUVmax) group (n=7) and 44.6 months (95% CI, 39.9-49.3 months) for the lower SUVmax group (n=29). OS in the higher SUVmax group (cut-off point, 6.1) or positive visual interpretation group was significantly shorter than that in the lower SUVmax or negative visual interpretation group (P<0.001 and P<0.05, respectively). CONCLUSIONS: The SUVmax and visual interpretation of HNSCC on post-IACR (18)F-FDG PET/CT can provide prognostic survival estimates.

Isolated prosopagnosia caused by damage to the right inferior longitudinal fasciculus: a case report.

Prosopagnosia is a cognitive disorder in which facial recognition is severely impaired despite normal vision and intelligence. Prosopagnosia was first reported in the 1800s, but its cause remains unclear. Although other neurological symptoms are often present, some patients have pure prosopagnosia. The bilateral occipital lobes are believed to be associated with symptoms. Recent brain imaging techniques have identified the right fusiform gyrus (rFG), located at the junction of the right occipital temporal lobe, as the affected region. In this report, we present a case of associative prosopagnosia with no concomitant symptoms in a 76-year-old man. Brain magnetic resonance imaging detected a subcortical hemorrhage in the right temporal lobe. Using tractography based on diffusion tensor imaging, we visualized atrophy of the right inferior longitudinal fasciculus (ILF). This is the first time tractography has been used to show a clear association between associative prosopagnosia and ILF damage projecting from the rFG.

Surface-based Analyses of Diffusional Kurtosis Imaging in Amyotrophic Lateral Sclerosis: Relationship with Onset Subtypes.

PURPOSE: Here, we aimed to characterize the cortical and subcortical microstructural alterations in the brains of patients with amyotrophic lateral sclerosis (ALS). In particular, we compared these features between bulbar-onset ALS (b-ALS) and limb-onset ALS (l-ALS). METHODS: Diffusion MRI data (b = 0, 700, 2000 ms/mm2, 1.7-mm isotropic voxel) from 28 patients with ALS (9 b-ALS and 19 l-ALS) and 17 healthy control subjects (HCs) were analyzed. Diffusional kurtosis imaging (DKI) metrics were sampled at the mid-cortical and subcortical surfaces. We used permutation testing with a nonparametric combination of mean diffusivity (MD), fractional anisotropy (FA), and mean kurtosis (MK) to assess intergroup differences over the cerebrum. We also carried out an atlas-based analysis focusing on Brodmann Area 4 and 6 (primary motor and premotor areas) and investigated the correlation between MRI metrics and clinical parameters. RESULTS: At both the mid-cortical and subcortical surfaces, b-ALS was associated with significantly greater MD, smaller FA, and smaller MK in the motor and premotor areas than HC. In contrast, the patients with l-ALS showed relatively moderate differences relative to HCs. The ALS Functional Rating Scale-Revised bulbar subscore was significantly correlated with the diffusion metrics in Brodmann Area 4. CONCLUSION: The distribution of abnormalities over the cerebral hemispheres and the more severe microstructural alteration in b-ALS compared to l-ALS were in good agreement with findings from postmortem histology. Our results suggest the feasibility of surface-based DKI analyses for exploring brain microstructural pathologies in ALS. The observed differences between b-ALS and l-ALS and their correlations with functional bulbar impairment support the clinical relevance of DKI measurement in the cortical and juxtacortical regions of patients with ALS.

Associations between Verbal Fluency and Asymmetry of White Matter Integrity in the Superior Longitudinal Fasciculus in At-Risk Mental States for Psychosis.

Verbal fluency is one of the most severely impaired components of cognitive function in schizophrenia and is also impaired in at-risk mental states (ARMSs) for psychosis. The aim of this study was to explore the markers of disease progression in subjects with ARMSs by comparing the association between the white matter integrity of the superior longitudinal fasciculus (SLF) and verbal fluency in subjects with ARMSs and healthy control (HC) subjects. The correlations of the fractional anisotropy (FA) values on diffusion tensor imaging (DTI) and the laterality index (LI) values of SLF branches I, II, and III with the verbal fluency performance were analyzed in right-handed subjects with ARMSs (ARMS group; n = 18) and HC subjects (HC group; n = 34) aged 18 to 40 years old. In the HC group compared with the ARMS group, the LI values suggested right lateralization of the SLF II and III. Letter fluency was significantly correlated with the LI of the SLF III in both the ARMS and HC groups. The regression coefficient (ß) of this correlation was calculated using the least squares method and yielded a positive number (73.857) in the ARMS group and a negative number (-125.304) in the HC group. The association of the rightward asymmetry of the SLF III with the verbal fluency performance observed in the HC group appeared to be lost in the ARMS group, and this could serve as one of the markers of the pathological progression to psychosis in patients with schizophrenia.