WM Abnormalities Research Articles

Dynamic Changes in Long-Standing Multiple Sclerosis Revealed by Longitudinal Structural Network Analysis Using Diffusion Tensor Imaging.

DTI can be used to derive conventional diffusion measurements, which can measure WM abnormalities in multiple sclerosis. DTI can also be used to construct structural brain networks and derive network measurements. However, few studies have compared their sensitivity in detecting brain alterations, especially in longitudinal studies. Therefore, in this study, we aimed to determine which type of measurement is more sensitive in tracking the dynamic changes over time in MS. Eighteen patients with MS were recruited at baseline and followed up at 6 and 12 months. All patients underwent MR imaging and clinical evaluation at 3 time points. Diffusion and network measurements were derived, and their brain changes were evaluated. None of the conventional DTI measurements displayed statistically significant changes during the follow-up period; however, the nodal degree, nodal efficiency, and nodal path length of the left middle frontal gyrus and bilateral inferior frontal gyrus, opercular part showed significant longitudinal changes between baseline and at 12 months, respectively. The nodal degree, nodal efficiency, and nodal path length of the left middle frontal gyrus and bilateral inferior frontal gyrus, opercular part may be used to monitor brain changes over time in MS.

Free water imaging in Parkinson's disease and atypical parkinsonian disorders.

Free water (FW)-corrected diffusion measures are more precise compared to standard diffusion measures. This study comprehensively evaluates FW and corrected diffusion metrics for whole brain white and deep gray matter (WM, GM) structures in patients with Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) and attempts to ascertain the probable patterns of WM abnormalities. Diffusion MRI was acquired for subjects with PD (n = 133), MSA (n = 25), PSP (n = 30) and matched healthy controls (HC) (n = 99, n = 24, n = 12). Diffusion metrics of FA, MD, AD, RD were generated and FW, corrected FA maps were calculated using a bi-tensor model. TBSS was carried out at 5000 permutations with significance at p < 0.05. For GM, diffusivity maps were extracted from the basal ganglia, and analyzed at an FDR with p < 0.05. Compared to HC, PD showed focal changes in FW. MSA showed changes in the cerebellum and brainstem, and PSP showed increase in FW involving supratentorial WM and midbrain. All three showed increased substantia nigra FW. MSA, PSP demonstrated increased FW in bilateral putamen. PD showed increased FW in left GP externa, and bilateral thalamus. Compared to HC, MSA had increased FW in bilateral GP interna, and left thalamic. PSP had an additional increase in FW of the right GP externa, right GP interna, and bilateral thalamus. The present study demonstrated definitive differences in the patterns of FW alterations between PD and atypical parkinsonian disorders suggesting the possibility of whole brain FW maps being used as markers for diagnosis of these disorders.

Incremental value of myocardial work analysis for detection of coronary artery disease during dipyridamole stress echocardiography

Abstract Funding Acknowledgements Type of funding sources: None. Background Dipyridamole stress-echocardiography (DipSE) relies on operator’s expertise and might have suboptimal diagnostic accuracy in identifying patients (pts) with single-vessel coronary artery disease (CAD). 2D strain, and, recently, myocardial work (MW) analysis, provide a more accurate evaluation of myocardial function, being able to detect subtle regional abnormalities. Purpose Aim of our study was to investigate whether MW analysis could have an additive role, when implemented to DipSE, in CAD detection. Methods We retrospectively enrolled 50 pts (20 M) who underwent DipSE followed, within one month, by coronary CT (CCT), in the absence of stress-induced WM abnormalities, or by invasive coronary angiography (ICA), when new WM abnormalities occurred. According to the presence of obstructive CAD (confirmed by ICA in any case), the population was subdivided into 2 groups: group 1 (with obstructive CAD: 34 pts) and group 2 (without obstructive CAD: 16 pts). After matching DipSE and CCT/ICA results, we further subdivided the population into three subgroups: 1 (true positives: 34 pts), 2A (false positives: 9 pts) and 2B (true negatives: 7 pts); no patients had a false negative DipSE result. Global longitudinal strain (GLS), work index (GWI), constructive work (GCW), waste work (GWW) and work efficiency (GWE) were calculated, at baseline, low and peak dose. Results In group 1, GLS increased at low and decreased at peak dose (p 0.015), while, in group 2, increased, mostly from low to peak dose (p&amp;lt; 0.001), Fig. 1. GWI and GCW, at low dose, decreased in group 1 (p 0.035 and p 0.009) whereas increased in group 2 (p 0.042 and p ns). GWW increased, at peak dose, in group 1 (p 0.003), whereas decreased in group 2 (p 0.047). GWE decreased, at peak dose, in group 1 (p 0.025), whereas increased in group 2 (p 0.001). When evaluating the subgroups (Fig. 1, right panels), we found that, in subgroup 2A, GLS increased at low and decreased at peak dose (p 0.015), similarly to subgroup 1 (at low dose p 0.011) and differently from subgroup 2B (from baseline to peak dose p 0.003). GWE, in subgroup 2A, increased at peak dose (p 0.023), differently from subgroup 1 (p 0.001) and similarly to subgroup 2B (at low dose: p 0.026; at peak dose: p 0.029). ROC analysis, for obstructive CAD, showed that GLS had a lower AUC (0.653) than GWW (0.735) and GWE (0.845), whereas GWI and GCW had, an AUC of 0.606 and 0.591, respectively (Fig. 2). A ≥ 0.5% GLS change (from low to peak dose) gained a sensitivity of 58%, a specificity of 67%, a positive predictive value (PPV) of 66% and a negative predictive value (NPV) of 64%. Conversely, a ≥ −1.5% GWE change (from low to peak dose) provided a sensitivity of 73%, a specificity of 84%, a PPV of 86% and NPV of 79%. Net reclassification improvement (NRI) for GWE was 0.049 (p 0.005). Conclusion MW analysis beyond GLS shows an additive role in the detection of CAD, thus improving diagnostic performance of DipSE.

White matter abnormalities in first-episode patients with depersonalization/derealization disorder: A tract-based spatial statistics study

BackgroundNeuroimaging studies on depersonalization / derealization disorder (DPD) have revealed that there are structural and functional alterations across numerous brain regions. However, to date, the exact white matter abnormalities that are associated with different clinical symptoms and cognitive impairments in first-episode, drug-naïve patients with DPD remain unclear. MethodsOverall, 25 first-episode, drug-naïve patients with DPD and 23 healthy controls were recruited and underwent DTI scans. The tract-based spatial statistics analysis was conducted in order to determine white matter microstructural changes between the two groups. Correlation analysis was conducted between the fractional anisotropy (FA) of abnormal WM fibers and the total score of the 30-item Cambridge Depersonalization Scale (CDS-30), cognitive assessments. ResultsPatients with DPD demonstrated higher FA in the right corpus callosum (CC), and posterior corona radiate (CR), compared to healthy controls. The FA in the right CC demonstrated a positive correlation with total score of CDS-30, numbing, unreality of self, perceptual alterations, and temporal disintegration, respectively. FA in the right CR region indicated a positive correlation with the total score of CDS-30, unreality of self, perceptual alterations, and temporal disintegration, respectively. Furthermore, FA in the right CR region was found to be negatively correlated with the Continuous Performance Test and the Stroop color-word test. ConclusionThe altered white matter microstructure and cognitive impairments of medication naïve DPD patients were observed. Abnormalities in the integrity of CC and CR were associated with severity of symptoms and cognitive impairments, which may provide a potential biomarker for clinical studies on DPD.

Multi-detector computed tomography and 3Tesla magnetic resonance imaging in assessment of COVID-19 intracranial complications

BackgroundThe novel worldwide coronavirus (COVID-19) pandemic, first appearing in Wuhan, China, has allured immense global attention. To our comprehension, this research work accommodates the largest isolation hospital-conducted cohort of coronavirus patients in which neuro-radiological complications were retrospectively assessed. To the present day, our full understanding of COVID-19 and its spectrum of diverse complications still remains insufficient. Moreover, the number of reported neurological complications albeit the global spread of the coronavirus pandemic is also widely lacking due to the constrained implementation of MR neuro-imaging in COVID-19 patients.ResultsForty-eight males and 26 females met the inclusion criteria, with a mean age 60.55 (ranged from 22 to 88 years old). The frequent clinical manifestation has impaired level of consciousness 55.4%. Most commonly recurring radiological findings were ischemic stroke 54.06% and parenchymal hematomas and hemorrhage 25.69%. Other less imaging brain findings were certain diagnostic entities, i.e., PRES, cerebral edema, leuko-encephalopathic WM abnormalities, microhemorrhages, vascular thrombosis and acute necrotizing encephalopathy. Soaring mortality rates correlated with serious neuro-radiological manifestations, being highest with infarction 57.5%, p = 0.908 and hemorrhage/hematomas 63.2%, p = 0.604.ConclusionsIntra-cranial complications were significantly detectable in COVID-19 infection and correlated with severity of illness. Outstanding higher mortality rates were associated with worsening neuro-radiological complications.

Impact of Brachial-Ankle Pulse Wave Velocity on Myocardial Work by Non-invasive Left Ventricular Pressure-Strain in Non-hypertensive and Hypertensive Patients With Preserved Left Ventricular Ejection Fraction.

ObjectiveData regarding the influence of arterial stiffness on myocardial work (MW) has been scarce. This study was performed to investigate the association between brachial-ankle pulse wave velocity (baPWV) and MW by non-invasive left ventricular pressure–strain in a population of non-hypertensive and hypertensive individuals.MethodsTwo hundred and eight participants (104 hypertensive and 104 non-hypertensive individuals) were prospectively enrolled into the study. All participants underwent conventional echocardiography, as well as 2D speckle-tracking echocardiography to assess MW by non-invasive left ventricular pressure–strain and global longitudinal strain (GLS). baPWV measurements were made at the same day as the echocardiography. Then, participants were categorized according to baPWV tertiles. Correlation between baPWV and MW were analyzed. Predicting ability of baPWV for abnormal WM was analyzed using receiver operating characteristic (ROC) curve.ResultsThe median baPWV from the low to high tertile groups were 1286.5 (1197.5–1343.5), 1490.0 (1444.5–1544.0), and 1803.8(1708.3–1972.0) cm/s, respectively. In simple linear regression analysis, baPWV had a significant positive association with global work index (GWI), global constructed work (GCW), and global wasted work (GWW), and a negative association with global work efficiency (GWE). The association remained significant after adjusting for major confounding factors in multiple linear regression analysis. The areas under the ROC curve of baPWV for predicting abnormal GWI, GCW, GWW, and GWE were 0.653, 0.666, 0.725, and 0.688, respectively (all p < 0.05).ConclusionsBaPWV is significantly associated with all four components of MW using non-invasive left ventricular pressure-strain method in a mixed population of non-hypertensive and hypertensive individuals.

Pretreatment Normal WM Magnetization Transfer Ratio Predicts Risk of Radiation Necrosis in Patients with Medulloblastoma.

Radiation necrosis, for which abnormal WM enhancement is a hallmark, is an uncommon complication of craniospinal irradiation in children with medulloblastoma. The magnetization transfer ratio measures macromolecular content, dominated by myelin in the WM. We investigated whether the pretreatment supratentorial (nonsurgical) WM magnetization transfer ratio could predict patients at risk for radiation necrosis after radiation therapy for medulloblastoma. Ninety-five eligible patients with medulloblastoma (41% female; mean age, 11.0 [SD, 5.4] years) had baseline balanced steady-state free precession MR imaging before proton or photon radiation therapy. Associations among baseline supratentorial magnetization transfer ratio, radiation necrosis (spontaneously resolving/improving parenchymal enhancement within the radiation field)3, age, and the presence of visible brain metastases were explored by logistic regression and parametric/nonparametric techniques as appropriate. Twenty-three of 95 (24.2%) children (44% female; mean age, 10.7 [SD, 6.7] years) developed radiation necrosis after radiation therapy (19 infratentorial, 1 supratentorial, 3 both). The mean pretreatment supratentorial WM magnetization transfer ratio was significantly lower in these children (43.18 versus 43.50, P = .03). There was no association between the supratentorial WM magnetization transfer ratio and age, sex, risk/treatment stratum, or the presence of visible brain metastases. A lower baseline supratentorial WM magnetization transfer ratio may indicate underlying structural WM susceptibility to radiation necrosis and may identify children at risk for developing radiation necrosis after craniospinal irradiation for medulloblastoma.

Early oxygen levels contribute to brain injury in extremely preterm infants

BackgroundExtremely low gestational age newborns (ELGANs) are at risk of neurodevelopmental impairments that may originate in early NICU care. We hypothesized that early oxygen saturations (SpO2), arterial pO2 levels, and supplemental oxygen (FiO2) would associate with later neuroanatomic changes.MethodsSpO2, arterial blood gases, and FiO2 from 73 ELGANs (GA 26.4 ± 1.2; BW 867 ± 179 g) during the first 3 postnatal days were correlated with later white matter injury (WM, MRI, n = 69), secondary cortical somatosensory processing in magnetoencephalography (MEG-SII, n = 39), Hempel neurological examination (n = 66), and developmental quotients of Griffiths Mental Developmental Scales (GMDS, n = 58).ResultsThe ELGANs with later WM abnormalities exhibited lower SpO2 and pO2 levels, and higher FiO2 need during the first 3 days than those with normal WM. They also had higher pCO2 values. The infants with abnormal MEG-SII showed opposite findings, i.e., displayed higher SpO2 and pO2 levels and lower FiO2 need, than those with better outcomes. Severe WM changes and abnormal MEG-SII were correlated with adverse neurodevelopment.ConclusionsLow oxygen levels and high FiO2 need during the NICU care associate with WM abnormalities, whereas higher oxygen levels correlate with abnormal MEG-SII. The results may indicate certain brain structures being more vulnerable to hypoxia and others to hyperoxia, thus emphasizing the role of strict saturation targets.ImpactThis study indicates that both abnormally low and high oxygen levels during early NICU care are harmful for later neurodevelopmental outcomes in preterm neonates.Specific brain structures seem to be vulnerable to low and others to high oxygen levels.The findings may have clinical implications as oxygen is one of the most common therapies given in NICUs.The results emphasize the role of strict saturation targets during the early postnatal period in preterm infants.

In Vivo Evaluation of White Matter Abnormalities in Children with Duchenne Muscular Dystrophy Using DTI.

Duchenne muscular dystrophy is an X-linked disorder characterized by progressive muscle weakness and prominent nonmotor manifestations, such as a low intelligence quotient and neuropsychiatric disturbance. We investigated WM integrity in patients with Duchenne muscular dystrophy using DTI. Fractional anisotropy and mean, axial, and radial diffusivity (DTI measures) were used to assess WM microstructural integrity along with neuropsychological evaluation in patients with Duchenne muscular dystrophy (n = 60) and controls (n = 40). Exon deletions in the DMD gene were confirmed using multiplex ligation-dependent probe amplification. Patients were classified into proximal (DMD Dp140+) and distal (DMD Dp140-) subgroups based on the location of the exon deletion and expression of short dystrophin Dp140 isoform. WM integrity was examined using whole-brain Tract-Based Spatial Statistics and atlas-based analysis of DTI data. The Pearson correlation was performed to investigate the possible relationship between neuropsychological scores and DTI metrics. The mean ages of Duchenne muscular dystrophy and control participants were 8.0 ± 1.2 years and 8.2 ± 1.4 years, respectively. The mean age at disease onset was 4.1 ± 1.8 years, and mean illness duration was 40.8 ± 25.2 months. Significant differences in neuropsychological scores were observed between the proximal and distal gene-deletion subgroups, with more severe impairment in the distal-deletion subgroup (P < .05). Localized fractional anisotropy changes were seen in the corpus callosum, parietal WM, and fornices in the patient subgroup with Dp140+, while widespread changes were noted in the Dp140- subgroup. The Dp140+ subgroup showed increased axial diffusivity in multiple WM regions relative to the Dp140- subgroup. No significant correlation was observed between clinical and neuropsychological scores and diffusion metrics. Widespread WM differences are evident in patients with Duchenne muscular dystrophy relative to healthy controls. Distal mutations in particular are associated with extensive WM abnormalities and poor neuropsychological profiles.

Long-term prognostic value of stress myocardial perfusion echocardiography in patients with coronary artery disease: a meta-analysis.

To evaluate the prognostic value of myocardial perfusion (MP) imaging during contrast stress echocardiography (cSE) in patients with known or suspected coronary artery disease (CAD). A search in PubMed, Embase databases, and the Cochrane library was conducted through May 2019. The Cochran Q statistic and the I2 statistic were used to assess heterogeneity, and the results were analysed by RevMan V5.3 and Stata V15.1 software. Twelve studies (seven dipyridamole and five exercise/dobutamine) without evidence of patient overlap (same institution publishing results over a similar time period) enrolling 5953 subjects (47% female, 8-80 months of follow-up) were included in the analysis. In all studies, total adverse cardiovascular events were defined as either cardiac death, non-fatal myocardial infarction (NFMI), or need for urgent revascularization. Hazard ratios (HRs) revealed that a MP abnormality [pooled HR 4.75; 95% confidence interval (CI) 2.47-9.14] was a higher independent predictor of total events than abnormal wall motion (WM, pooled HR 2.39; 95% CI 1.58-3.61) and resting left ventricular ejection fraction (LVEF, pooled HR 1.92; 95% CI 1.44-2.55) with significant subgroup differences (P = 0.002 compared with abnormal WM and 0.01 compared with abnormal LVEF). Abnormal MP was associated with higher risks for death [Risk ratio (RR) 5.24; 95% CI 2.91-9.43], NFMI (RR 3.09; 95% CI 1.84-5.21), and need for coronary revascularization (RR 16.44; 95% CI 6.14-43.99). MP analysis during stress echocardiography is an effective prognostic tool in patients with known or suspected CAD and provides incremental value over LVEF and WM in predicting clinical outcomes.

Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes

White matter hyperintensity (WMH) is a common finding in aging population and considered to be a contributor to cognitive decline. Our study aimed to characterize the spatial patterns of WMH in different severities and explore its impact on cognition and brain microstructure in non-demented elderly. Lesions were both qualitatively (Fazekas scale) and quantitatively assessed among 321 community-dwelled individuals with MRI scanning. Voxel- and atlas-based analyses of the whole-brain white matter microstructure were performed. The WMH of the same severities was found to occur uniformly with a specific pattern of lesions. The severity of WMH had a significant negative association with the performance of working and episodic memory, beginning to appear in Fazekas 3 and 4. The white matter tracts presented significant impairments in Fazekas 3, which showed brain-wide changes above Fazekas 4. Lower FA in the superior cerebellar peduncle and left posterior thalamic radiation was mainly associated with episodic memory, and the middle cerebellar peduncle was significantly associated with working memory. These results support that memory is the primary domain to be affected by WMH, and the effect may potentially be influenced by tract-specific WM abnormalities. Fazekas scale 3 might be the critical stage predicting a future decline in cognition.

Brain white matter abnormalities associated with copy number variants.

White matter (WM) signal abnormalities are demonstrated in various neurodevelopmental disorders on brain magnetic resonance imaging (MRI). The pattern of WM abnormalities can aid in the diagnostic process. This study aims to characterize the WM changes found in microdeletion/microduplication syndromes. Thirteen patients with neurodevelopmental disorders due to copy number variations were collected from a cohort of children with evidence of WM abnormalities on brain MRI, in two medical centers. A pediatric neuroradiologist blindly interpreted the MRI scans. Clinical and genetic findings were retrospectively extracted from the medical records. WM changes included: multifocal (10/13) periventricular (12/13) and subcortical (5/13) signal abnormalities and WM volume loss (6/13). Dysgenesis of the corpus callosum was depicted in 12/13. The main clinical features were: global developmental delay (13/13), hypotonia (11/13), epilepsy (10/13), dysmorphic features (9/13), microcephaly (6/13), short stature (6/13), and systemic involvement (6/13). We showed that different chromosomal micro-rearrangement syndromes share similar MRI patterns of nonspecific multifocal predominantly periventricular WM changes associated with corpus callosum dysgenesis with or without WM and gray matter loss. Hence, the association of these features in a patient evaluated for global developmental delay/intellectual disability suggests a chromosomal micro-rearrangement syndrome, and a chromosomal microarray analysis should be performed.

Role of glia in prefrontal white matter abnormalities in first episode psychosis or mania detected by diffusion tensor spectroscopy

BackgroundWhite matter (WM) abnormalities are amongst the most commonly described neuroimaging findings in patients with psychotic disorders including schizophrenia (SZ) and bipolar disorder (BD), and may be central to pathophysiology. Few studies have directly compared WM abnormalities in patients with SZ and BD in the first episode of illness, and no studies to date have attempted to separate abnormalities of axon and myelin using complementary MRI techniques. MethodsWe examined WM abnormalities in young adults with SZ (n = 19) or BD (n = 16) within the first year of illness onset, and healthy controls (n = 22) using a combination of diffusion tensor spectroscopy to measure NAA, creatine (Cr), and choline (Cho), and magnetization transfer ratio (MTR). MTR reflects myelin content, NAA diffusion is neuron specific, and Cr and Cho diffusion reflect both neuron and glial signal. ResultsWe found no differences in MTR or NAA ADC in either patient group compared to controls, but significant elevations of both Cr and Cho diffusion in patients with SZ, and elevations of Cho diffusion in patients with BD. Elevations in Cr and Cho diffusion in the absence of NAA diffusion abnormalities indicate that the aberrant signal arises in glia. ConclusionsGlial abnormalities were present and detectable by the first episode of psychosis, whereas major abnormalities in axon and myelin were not. Examination of these neurobiological markers early in the course of illness may clarify the neuroprogressive nature of these distinct aspects of WM, and their associations with early clinical phenotypes.

Advances in imaging of brain abnormalities in neuromuscular disease.

Brain atrophy, white matter abnormalities, and ventricular enlargement have been described in different neuromuscular diseases (NMDs). We aimed to provide a comprehensive overview of the substantial advancement of brain imaging in neuromuscular diseases by consulting the main libraries (Pubmed, Scopus and Google Scholar) including the more common forms of muscular dystrophies such as dystrophinopathies, dystroglycanopathies, myotonic dystrophies, facioscapulohumeral dystrophy, limb-girdle muscular dystrophy, congenital myotonia, and congenital myopathies. A consistent, widespread cortical and subcortical involvement of grey and white matter was found. Abnormalities in the functional connectivity in brain networks and metabolic alterations were observed with positron emission tomography (PET) and single photon emission computed tomography (SPECT). Pathological brain changes with cognitive dysfunction seemed to be frequently associated in NMDs. In particular, in congenital muscular dystrophies (CMDs), skeletal muscular weakness, severe hypotonia, WM abnormalities, ventricular dilatation and abnormalities in cerebral gyration were observed.In dystroglycanopathy 2I subtype (LGMD2I), adult patients showed subcortical atrophy and a WM periventricular involvement, moderate ventriculomegaly, and enlargement of subarachnoid spaces. Correlations with clinical features have been observed with brain imaging characteristics and alterations were prominent in congenital or childhood onset cases. In myotonic dystrophy type 2 (DM2) symptoms seem to be less severe than in type 1 (DM1).In Duchenne and Becker muscular dystrophies (DMD, BMD) cortical atrophy is associated with minimal ventricular dilatation and WM abnormalities.Late-onset glycogenosis type II (GSD II) or Pompe infantile forms are characterized by delayed myelination. Only in a few cases of oculopharyngeal muscular dystrophy (OPMD) central nervous system involvement has been described and associated with executive functions impairment.

Peak width of skeletonized mean diffusivity (PSMD) as marker of widespread white matter tissue damage in multiple sclerosis

BackgroundPeak width of skeletonized mean diffusivity (PSMD) is a novel and fully automated, MRI biomarker, which has shown clinical relevance in cerebral small vessel diseases (SVD). We aimed here to assess PSMD levels across the brain of patients with multiple sclerosis (MS), in comparison to normal controls (NC) and patients with CADASIL, a genetically defined form of severe SVD. MethodsWe assessed PSMD in relapsing-remitting (RR) MS patients (n = 47) in comparison to age-matched CADASIL patients (n = 25) and NC (n = 28). Diffusion Tensor Imaging data were acquired on 1.5T MR clinical scanner to automatically compute PSMD through “skeletonization” of WM tracts and diffusion histograms. ResultsRRMS had lower WM lesion volume (LV) than CADASIL (8.6 ± 8.2 vs 24.4 ± 17.4 cm3, p < 0.001). After correction for LV, PSMD values in MS were higher than in CADASIL patients (adjusted mean values: 4.5 vs 3.9 × 10−4 mm2/s, p = 0.03) and in both patient groups were higher than in NC (2.8 ± 0.3 × 10−4 mm2/s, p < 0.001). PSMD values correlated with LV in both patient groups (r = 0.8, p < 0.001 in MS; r = 0.6, p = 0.002 in CADASIL). ConclusionsIn both patient groups, PSMD was higher than in NC and closely correlated with LV, suggesting sensitivity in assessing brain tissue damage in these disorders. In MS patients, PSMD levels were higher than in CADASIL patients, despite the lower LV. This might be related to more severe normal-appearing WM abnormalities occurring in the MS brains. This novel, fully automated, MRI metric may represent a useful marker for a robust quantification of the diffuse WM tissue damage in MS.

White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: Combined DTI and immunological investigation in the different phases of bipolar disorder

BackgroundWhite matter (WM) microstructural abnormalities and, independently, signs of immunological activation were consistently demonstrated in bipolar disorder (BD). However, the relationship between WM and immunological alterations as well as their occurrence in the various phases of BD remain unclear. MethodIn 60 type I BD patients – 20 in manic, 20 in depressive, 20 in euthymic phases – and 20 controls we investigated: (i) diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) using a tract-based spatial statistics (TBSS) approach; (ii) circulating T cell subpopulations frequencies, as well as plasma levels of different cytokines; (iii) potential relationships between WM and immunological data. ResultsWe found: (i) a significant widespread combined FA-RD alteration mainly in mania, with involvement of the body of corpus callosum (BCC) and superior corona radiata (SCR); (ii) significant increase in CD4+ T cells as well as significant decrease in CD8+ T cells and their subpopulations effector memory (CD8+ CD28-CD45RA-), terminal effector memory (CD8+ CD28-CD45RA+) and CD8+ IFNγ+ in mania; (iii) a significant relationship between WM and immunological alterations in the whole cohort, and a significant correlation of FA-RD abnormalities in the BCC and SCR with reduced frequencies of CD8+ terminal effector memory and CD8+ IFNγ+ T cells in mania only. ConclusionsOur data show a combined occurrence of WM and immunological alterations in mania. WM abnormalities highly correlated with reduction in circulating CD8+ T cell subpopulations that are terminally differentiated effector cells prone to tissue migration, suggesting that these T cells could play a role in WM alteration in BD.

Regional Susceptibility to Chronic Anemia in WM Microstructure Using Diffusion Tensor Imaging

Introduction: White matter strokes are a major concern for patients with sickle cell disease and other forms of anemia. SCD patients are known to have diffuse white matter volume loss, abnormal WM microstructure, silent strokes, and poor neurocognitive function. Similar neurological abnormalities have been described in thalassemia intermedia. Low levels of hemoglobin have been associated with risk of silent cerebral infarctions across patient populations with chronic anemia and severe anemia may increase the risk for cerebral vascular accidents. In this current study, we use MRI brain mapping techniques to explore the relationship between a wide range of hemoglobin levels and WM neural tissue properties.Methods: 16 SCD patients (age=26.1 ± 10.3; F=9, M=7; hemoglobin=9.4 ± 2.1), 8 patients with non-sickle anemia (age=23.6 ± 7.4; F=4, M=4; hemoglobin=12.2 ± 3.2), and 15 control subjects (age=22.8 ± 7.2; F=10, M=5; hemoglobin=13.2 ± 1.3) were recruited with informed consent or assent; the study was approved by the Institutional Review Board at Children’s Hospital Los Angeles (CCI#11-00083). Exclusion criteria included pregnancy, previous overt stroke, acute chest, or pain crisis hospitalization within one month. MRI data were acquired on a 3T Philips Achieva (v.3.2.1) using an 8-channel head coil.3D T1-weighted images (TE =3.8ms TR =8.3ms; resolution = 1mm3) were pre-processed using BrainSuite (brainsuite.org) and registered to a common atlas space using Surface Volume Registration (SVReg15a). Diffusion weighted images (TE = 2.5ms; TR = 4.8ms; 2.5mm isotropic voxels) included 30 diffusion-encoding directions at b-value=1000m/s2 and a reverse-gradient b=0. Fieldmaps were estimated using FSL's topup module. BrainSuite Diffusion Pipeline (BDP15a) performed distortion correction, co-registration to T1-weighted images, and diffusion tensor modeling. Voxel-wise calculations of DTI metrics including fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were transferred to the common atlas space. Pearson correlations were performed using BrainSuite Statistics Toolbox.Results: Hemoglobin was correlated to FA, AD, and, RD in multiple brain regions after controlling for age and sex (Figure 1) The colorbar represents the r-value for the correlations (red positive, blue negative) and only statistically significant values are displayed. Anemia was associated with increased RD and AD broadly over the brain (blue), including corpus callosum, subcortical nuclei, and frontal and parietal white matter. These regions represent classic "watershed" areas that are the primary targets of silent strokes in sickle cell disease, hypertension, aging, and obstructive sleep apnea. FA changes were more modest in extent, but also occurred in areas classically associated with silent stroke.Conclusion: Our study suggests that the severity of anemia, rather than the type of anemia, is the primary risk factor for white matter damage. Low hemoglobin concentration correlated to increases in RD and AD, indicative of demyelination and axonal degeneration respectively. Interestingly, the regions of abnormal diffusivity parallel the pattern of regional vulnerability to stroke in SCD patients in previous literature (frontal lobe > parietal lobe, subcortical nuclei, > temporal lobe, >> occipital lobe and cerebellum). While silent strokes and abnormal diffusivity co-localize, the volume of infarcted tissue is much smaller, suggesting that changes in RD and AD are detecting preclinical white matter injury in anemic patients. We postulate that anemia, by depleting cerebrovascular reserve, leaves patients vulnerable to acute interruptions in supply or increases in metabolic demand. Our observations may have important implications for choosing set points for chronic transfusion therapy in anemic patients. [Display omitted] DisclosuresWood:Biomed Informatics: Consultancy; Biomed Informatics: Consultancy; Apopharma: Consultancy; Apopharma: Consultancy; AMAG: Consultancy; AMAG: Consultancy; Celgene: Consultancy; Celgene: Consultancy; World Care Clinical: Consultancy; World Care Clinical: Consultancy; Vifor: Consultancy; Vifor: Consultancy; Ionis Pharmaceuticals: Consultancy; Ionis Pharmaceuticals: Consultancy.

Ataxia Severity Correlates with White Matter Degeneration in Spinocerebellar Ataxia Type 7.

There is a scarcity of information on the effect of white matter degeneration in patients with spinocerebellar ataxia type 7. Therefore, we investigated the WM integrity in a large group of patients with spinocerebellar ataxia type 7 by using Tract-Based Spatial Statistics. Thirty-three patients with a molecular diagnosis of spinocerebellar ataxia type 7 and their age- and sex-matched healthy controls participated in this study. The patients' ataxia severity was evaluated with the Scale for the Assessment and Rating of Ataxia. Voxelwise analyses of diffusion metrics, including fractional anisotropy and mean diffusivity, were performed with Tract-Based Spatial Statistics. The correlation between WM abnormalities and ataxia severity was then calculated. Tract-Based Spatial Statistics analysis revealed WM abnormalities in the cerebellum and the cerebellar peduncles, as well as in other major cortical and subcortical pathways. Further analysis between the Scale for the Assessment and Rating of Ataxia score and WM mean diffusivity showed significant associations only in key areas related to motor control and visuospatial processing, including the cerebellar WM, the middle occipital WM, the superior cerebellar peduncle, and bilateral anterior thalamic radiation. No significant associations between fractional anisotropy and the Scale for the Assessment and Rating of Ataxia were found. These results suggest a significant contribution of local cerebellar and cerebellar-midbrain connections to ataxic impairment in spinocerebellar ataxia type 7. The results also suggest an involvement of cortical WM abnormalities including tracts within the occipital and frontal cortices. These findings contribute to a more comprehensive view of the clinical impact of the white matter degeneration in spinocerebellar ataxia type 7.

Discriminative analysis of schizophrenia using support vector machine and recursive feature elimination on structural MRI images.

Structural abnormalities in schizophrenia (SZ) patients have been well documented with structural magnetic resonance imaging (MRI) data using voxel-based morphometry (VBM) and region of interest (ROI) analyses. However, these analyses can only detect group-wise differences and thus, have a poor predictive value for individuals. In the present study, we applied a machine learning method that combined support vector machine (SVM) with recursive feature elimination (RFE) to discriminate SZ patients from normal controls (NCs) using their structural MRI data. We first employed both VBM and ROI analyses to compare gray matter volume (GMV) and white matter volume (WMV) between 41 SZ patients and 42 age- and sex-matched NCs. The method of SVM combined with RFE was used to discriminate SZ patients from NCs using significant between-group differences in both GMV and WMV as input features. We found that SZ patients showed GM and WM abnormalities in several brain structures primarily involved in the emotion, memory, and visual systems. An SVM with a RFE classifier using the significant structural abnormalities identified by the VBM analysis as input features achieved the best performance (an accuracy of 88.4%, a sensitivity of 91.9%, and a specificity of 84.4%) in the discriminative analyses of SZ patients. These results suggested that distinct neuroanatomical profiles associated with SZ patients might provide a potential biomarker for disease diagnosis, and machine-learning methods can reveal neurobiological mechanisms in psychiatric diseases.

Disorganization of white matter architecture in major depressive disorder: a meta-analysis of diffusion tensor imaging with tract-based spatial statistics

White matter (WM) abnormalities have long been suspected in major depressive disorder (MDD). Tract-based spatial statistics (TBSS) studies have detected abnormalities in fractional anisotropy (FA) in MDD, but the available evidence has been inconsistent. We performed a quantitative meta-analysis of TBSS studies contrasting MDD patients with healthy control subjects (HCS). A total of 17 studies with 18 datasets that included 641 MDD patients and 581 HCS were identified. Anisotropic effect size-signed differential mapping (AES-SDM) meta-analysis was performed to assess FA alterations in MDD patients compared to HCS. FA reductions were identified in the genu of the corpus callosum (CC) extending to the body of the CC and left anterior limb of the internal capsule (ALIC) in MDD patients relative to HCS. Descriptive analysis of quartiles, sensitivity analysis and subgroup analysis further confirmed these findings. Meta-regression analysis revealed that individuals with more severe MDD were significantly more likely to have FA reductions in the genu of the CC. This study provides a thorough profile of WM abnormalities in MDD and evidence that interhemispheric connections and frontal-striatal-thalamic pathways are the most convergent circuits affected in MDD.