Ex-Vivo Hippocampus Segmentation Using Diffusion-Weighted MRI

Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects’ sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development.

BackgroundIt is known that blood levels of neurofilament light (NF-L) and diffusion-weighted magnetic resonance imaging (DW-MRI) are both associated with outcome of patients with mild traumatic brain injury (mTBI). Here, we sought to examine the association between admission levels of plasma NF-L and white matter (WM) integrity in post-acute stage DW-MRI in patients with mTBI.MethodsNinety-three patients with mTBI (GCS ≥ 13), blood sample for NF-L within 24 h of admission, and DW-MRI ≥ 90 days post-injury (median = 229) were included. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized WM tracts of the whole brain. Outcome was assessed using the Extended Glasgow Outcome Scale (GOSE) at the time of imaging. Patients were divided into CT-positive and -negative, and complete (GOSE = 8) and incomplete recovery (GOSE < 8) groups.ResultsThe levels of NF-L and FA correlated negatively in the whole cohort (p = 0.002), in CT-positive patients (p = 0.016), and in those with incomplete recovery (p = 0.005). The same groups showed a positive correlation with mean MD, AD, and RD (p < 0.001—p = 0.011). In CT-negative patients or in patients with full recovery, significant correlations were not found.ConclusionIn patients with mTBI, the significant correlation between NF-L levels at admission and diffusion tensor imaging (DTI) measurements of diffuse axonal injury (DAI) over more than 3 months suggests that the early levels of plasma NF-L may associate with the presence of DAI at a later phase of TBI.

BackgroundWe hypothesized that the integrity of white matter might be related to the severity of freezing of gait in age-related white matter changes.MethodsTwenty subjects exhibiting excessive hyperintensities in the periventricular and deep white matter were recruited. The subjects underwent the Freezing of Gait Questionnaire, computerized gait analyses, and diffusion tensor magnetic resonance imaging. Images of axial, radial and mean diffusivity, and fractional anisotropy were calculated as indices of white matter integrity and analyzed with tract-based spatial statistics.ResultsThe fractional anisotropy, mean, axial and radial diffusivity averaged across the whole white matter structure were all significantly correlated with Freezing of Gait Questionnaire scores. Regionally, a negative correlation between Freezing of Gait Questionnaire scores and fractional anisotropy was found in the left superior longitudinal fasciculus beneath the left premotor cortex, right corpus callosum, and left cerebral peduncle. The scores of the Freezing of Gait Questionnaire were positively correlated with mean diffusivity in the left corona radiata and right corpus callosum, and with both axial and radial diffusivity in the left corona radiata. The white matter integrity in these tracts (except the corpus callosum) showed no correlation with cognitive or other gait measures, supporting the specificity of those abnormalities to freezing of gait.ConclusionDivergent pathological lesions involved neural circuits composed of the cerebral cortex, basal ganglia and brainstem, suggesting that freezing of gait has a multifactorial nature.

Objective: To study the alteration of the optic radiations in patients with primary open-angle glaucoma (POAG) by diffusion tensor imaging (DTI) and tractography, and to reveal the correlation between the DTI derived parameters and the severity of the disease. Methods: A total of 24 patients with POAG and 20 age- and gender-matched healthy controls were enrolled in this study from January 2011 to June 2013.All subjects underwent ophthalmoscopy, standard automatic perimetry, intraocular pressure measurement and MRI scanning.All the eyes of POAG patients were evaluated by Hodapp-Anderson-Parrish (HAP) system.Then the stages of bilateral eyes were added together to evaluate the disease severity.Tractography was used to measure the fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) of the optic radiations of these subjects.The results of the two groups were compared.Partial correlation was then used to reveal the correlation between these derived DTI parameters and the severity of POAG. Results: Compared with health controls, POAG patients showed significant decreased FA (t=-3.299, P=0.002) and AD (t=-2.485, P=0.013), increased RD (t=2.365, P=0.018) in optic radiation .The alteration of MD was not significant (t=0.719, P=0.454). Mean FA values of the optic radiations were negatively correlated with POAG stages (r=-0.643, P= 0.001), while mean RD values (r=0.570, P= 0.004) and mean MD values (r= 0.448, P= 0.028) were positively correlated with POAG stages.No correlation between AD values and severity of POAG was found. Conclusion: In the optic radiations of POAG patients, the FA values and AD values decrease, while RD values increase, indicating the fiber integrity changes.The alterations of FA, RD and MD are correlated with disease severity.

Diffusion tensor imaging of rectal carcinoma: Clinical evaluation and its correlation with histopathological findings

For humans and non-human primates, the alteration of the visual pathway’s white matter fibers after visual deprivation has been partially explored. However, the changes in the optic tracts after the transection of the optic nerve have not been well characterized. In the current study, we attempted to investigate the differences in optic tracts between normal and unilateral optic nerve transected macaque monkeys using diffusion tensor imaging (DTI). Four healthy neonatal macaque monkeys were randomly divided into 2 groups, with 2 in each group. Group A served as a control group, and Group B underwent unilateral (right eye) optic nerve transection to produce monocular blindness. Sixteen months (Group B16M) and thirty-two months (Group B32M) after optic nerve transection, diffusion tensor imaging was performed on all monkeys. Then, we compared fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in bilateral optic tracts between Group A and Group B and between Group B16M and Group B32M. In both Group B16M and Group B32M, when compared with normal monkeys in Group A, FA was decreased and MD, AD and RD were increased in the bilateral optic tracts of monkeys with monocular blindness. Furthermore, compared with Group B16M, FA was reduced and MD, AD, RD were more obviously increased in the bilateral optic tracts of Group B32M, and noticeable differences in MD, AD and RD were found between the left and right optic tracts in group B32M. We believe that the results of this study would be helpful in investigation of the histological abnormalities of the integrity damage, axonal degeneration and demyelination of optic tracts in macaque monkeys with monocular blindness by DTI parameters in noninvasively and quantitatively.

Cognitive decline in survivors of medulloblastoma is commonly attributed to radiation- and chemotherapy-induced brain microstructural alterations. Factors preceding this adjuvant therapy, such as disrupted brain development or resection surgery, may affect brain microstructure but have not been thoroughly explored in medulloblastoma. The aim of this study was to assess cortical thickness and microstructural integrity of the cerebrum prior to adjuvant therapy in medulloblastoma patients. Cross-sectional image data were acquired of medulloblastoma patients (n = 30) after surgery but before adjuvant therapy and compared with data from healthy controls (n = 35) matched for age range (12-22 years). Biomarkers of microstructural integrity include fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity. Thickness, surface area and volume were estimated for parcels of neocortex to evaluate potential morphology differences. Participants with medulloblastoma showed increased diffusivity parameters (mean, axial and radial diffusivity) and decreased fractional anisotropy, within nearly all white and grey matter parcels of the cerebrum, compared with healthy controls. Medulloblastoma participants additionally showed decreased cortical thickness in sub-regions of frontal, parietal, temporal and paracentral cortex. Broad cerebral microstructural alterations in medulloblastoma patients following surgery but before initiation of radiation or chemotherapy suggest that cerebellar insult, by tumour development or tumour resection, likely contributes to compromised integrity of cerebral grey and white matter. Locations of cortical thinning suggest that cerebellar insult may impair normal growth in cerebral regions responsible for executive function, language and attention-cognitive domains typically affected in medulloblastoma survivors.

Objective: The objective of this study was to observe the correlation between multiple quantitative parameters of magnetic resonance diffusion kurtosis imaging and expression of proliferation-related antigen Ki-67 in nasopharyngeal carcinoma. Methods: The imaging data of 25 cases receiving 1.5 T magnetic resonance imaging and pathologically diagnosed as nasopharyngeal carcinoma were retrospectively analyzed. They were divided into Ki-67 high-expression group (n=13) and low-expression group (n=12). Diffusion kurtosis imaging parameters in parenchymal lesions were measured by 2 observers. The consistency of measurement results of the 2 observers was detected using intraclass correlation coefficient. The efficiency of differential diagnosis was assessed using receiver operating characteristic curve. The correlation between each parameter and Ki-67 expression index was explored through the Pearson&amp;rsquo;s analysis. Results: The consistency of parameters of lesions measured by 2 observers was good in the 2 groups (intraclass correlation coefficient &amp;gt; 0.75). In the Ki-67 high-expression group, mean kurtosis, axial kurtosis, and radial kurtosis were higher, while mean diffusivity, axial diffusivity, and radial diffusivity were lower than those in the Ki-67 low-expression group (P &amp;lt; .05). Area under the curve values of mean kurtosis, axial kurtosis, radial kurtosis, mean diffusivity, axial diffusivity, and radial diffusivity for predicting high Ki-67 expression were 0.984, 0.922, 0.899, 0.903, 0.974, and 0.878, respectively. Mean kurtosis, axial kurtosis, and radial kurtosis were positively correlated with Ki-67 expression index, while mean diffusivity, axial diffusivity, and radial diffusivity were negatively correlated with this index (P &amp;lt; .05). Conclusion: The values of mean kurtosis, axial kurtosis, radial kurtosis, mean diffusivity, axial diffusivity, and radial diffusivity in the diffusion kurtosis imaging sequence are correlated with Ki-67 expression in nasopharyngeal carcinoma, and they have the potential to reflect the proliferation degree of nasopharyngeal carcinoma cells. Mean kurtosis is the optimal parameter. Cite this article as: Wu Y, Huang L, Li B, Li H. Correlation between diagnostic value of diffusion kurtosis imaging for nasopharyngeal carcinoma and ki-67 expression. B-ENT. 2023;19(2):69-73.

Simultaneous multi-slice (SMS) echo-planar imaging has had a huge impact on the acceleration and routine use of diffusion-weighted MRI (DWI) in neuroimaging studies in particular the human connectome project; but also holds the potential to facilitate DWI of moving subjects, as proposed by the new technique developed in this paper. We present a novel registration-based motion tracking technique that takes advantage of the multi-plane coverage of the anatomy by simultaneously acquired slices to enable robust reconstruction of neural microstructure from SMS DWI of moving subjects. Our technique constitutes three main components: 1) motion tracking and estimation using SMS registration, 2) detection and rejection of intra-slice motion, and 3) robust reconstruction. Quantitative results from 14 volunteer subject experiments and the analysis of motion-corrupted SMS DWI of 6 children indicate robust reconstruction in the presence of continuous motion and the potential to extend the use of SMS DWI in very challenging populations.

BackgroundDiffusion tensor imaging (DTI) can separate subjective cognitive decline (SCD) participants who progress to mild cognitive impairment and those who do not 1. We explored the effect age and memory performance has on DTI measures in SCD and controls in the hippocampal cingulum bundle, which is typically affected early in the course of Alzheimer’s disease2.Method325 participants Cam‐CAN 3 (127 SCD) older than 55 were included in the analysis. Diffusion imaging data was collected on a 3T Siemens TIM Trio scanner with a 32‐channel head coil for 0, 1000 and 2000 s/mm2 b‐values and 30 gradient directions. Preprocessing and calculation of the DTI metrics fractional anisotropy (FA, mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) were completed using MRTrix3, FSL and MATLAB. The hippocampal cingulum bundle regions of interest (ROIs) were extracted from the ICBM‐DTI‐81 atlas. Memory was assessed using the delayed story recall (DSR) task from WMS‐III. Linear regression models were completed in R. Gender was included as a nuisance variable.ResultThere were no differences in gender or age distribution between cohorts, however participants with SCD had a 14% lower DSR score (Table 1). There was a significant interaction effect between age and cohort in MD, AxD, and RD (Figure 1), as well as between memory and age in AxD (Figure 2). In post‐hoc analyses, compared to controls, the SCD group showed a stronger correlation with age in MD, AxD, and RD (Figure 1) while participants with worse memory showed a stronger correlation with age in MD (Figure 2), indicating an accelerated aging effect.ConclusionParticipants with SCD and worse memory present with an accelerated aging effect, showing steeper variations in diffusion microstructure with age. Since SCD is likely to be a preclinical stage of Alzheimer’s disease, future work will analyze this effect with more advanced diffusion microstructure models to further elucidate the underlying pathophysiology.1. Selnes P, Aarsland D, Bjornerud A, et al. J Alzheimers Dis. 2013;33(3):723‐36.2. Jack Jr CR, Knopman DS, Jagust WJ, et al. The Lancet Neurology. 2013;12(2):207‐16.3. Shafto MA, Tyler LK, Dixon M, et al. BMC neurology. 2014;14(1):1‐25.

We aimed to determine the feasibility of using DKI to characterize pathological changes in nonarteritic anterior ischemic optic neuropathy (NAION) and to differentiate it from acute optic neuritis (ON). Orbital DKI was performed with a 3.0T scanner on 75 patients (51 with NAION and 24 with acute ON) and 15 healthy controls. NAION patients were further divided into early and late groups. The mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were calculated to perform quantitative analyses among groups; and receiver operating characteristic curve analyses were also performed to determine their effectiveness of differential diagnosis. In addition, correlation coefficients were calculated to explore the correlations of the DKI-derived data with duration of disease. The MK, RK, and AK in the affected nerves with NAION were significantly higher than those in the controls, while the trend of FA, RD, and AD was a decline; in acute ON patients, except for RD, which increased, all DKI-derived kurtosis and diffusion parameters were significantly lower than controls (all P < 0.008). Only AK and MD had statistical differences between the early and late groups. Except for MD (early group) and FA, all other DKI-derived parameters were higher in NAION than in acute ON; and parameters in the early group showed better diagnostic efficacy in differentiating NAION from acute ON. Correlation analysis showed that time was negatively correlated with MK, RK, AK, and FA and positively correlated with MD, RD, and AD (all P < 0.05). DKI is helpful for assessing the specific pathologic abnormalities resulting from ischemia in NAION by comparison with acute ON. Early DKI should be performed to aid in the diagnosis and evaluation of NAION.

The aims of this study were to compare, using diffusion tensor imaging (DTI) of the brainstem, microstructural integrity of the white matter in children with achondroplasia and age-matched participants and to correlate the severity of craniocervical junction (CCJ) narrowing and neurological findings with DTI scalars in children with achondroplasia. This study also aimed to assess the potential role of fibroblast growth factor receptor type 3 on white matter microstructure. Diffusion tensor imaging was performed using a 1.5T magnetic resonance scanner and balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements were obtained from regions of interest, sampled in each pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle, as well as in the lower brainstem and centrum semiovale, for fractional anisotropy and for mean, axial, and radial diffusivity. In addition, a severity score for achondroplasia was assessed by measuring CCJ narrowing. Eight patients with achondroplasia (seven males, one female; mean age 5y 6mo, range 1y 1mo-15y 1mo) and eight age- and sex-matched comparison participants (mean age 5y 2mo, range 1y 1mo-14y 11mo) were included in this study. Fractional anisotropy was lower and mean diffusivity and radial diffusivity were higher in the lower brainstem of patients with achondroplasia than in age-matched comparison participants. The CST and middle cerebellar peduncle of the participants showed increases in mean, axial, and radial diffusivity. Fractional anisotropy in the lower brainstem was negatively correlated with the degree of CCJ narrowing. No differences in the DTI metrics of the centrum semiovale were observed between the two groups. The reduction in fractional anisotropy and increase in diffusivities in the lower brainstem of participants with achondroplasia may reflect secondary encephalomalacic degeneration and cavitation of the affected white matter tracts as shown by histology. In children with achondroplasia, DTI may serve as a potential biomarker for brainstem white matter injury and aid in the care and management of these patients.

PurposeTransfusion-dependent thalassemia (TDT) is associated with iron accumulation in the body and an increased tendency for thrombosis. With the increased life expectancy in these patients, the detection of neurocognitive complications has gained importance. This study investigates the microstructural changes in TDT patients using advanced diffusion MRI techniques and their relationship with laboratory parameters.MethodsThe study included 14 TDT patients and 14 control subjects. Tract-based spatial statistics (TBSS) were used to examine differences in DTI parameters such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in thalassemia patients using multi-shell DWI images. The mean kurtosis (MK) difference was investigated using diffusion kurtosis imaging. Fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC) differences were examined using fixel-based analysis. In the patient group, correlative tractography was used to investigate the relationship between DTI parameters and platelet (PLT) and ferritin levels.ResultsIncrease in RD and MD was observed, particularly in the white matter tracts of the corona radiata in patient group. Additionally, an increase in AD was detected in a limited area. Correlative tractography in thalasemia patients showed a positive correlation between increases in RD, MD, and AD with PLT and ferritin. Fixel-based analysis demonstrated a dispersed distribution in white matter fibers, with a more pronounced decrease in FD, FC, and FDC in the internal capsule.ConclusionThere is widespread involvement in the white matter and fiber tracts in thalassemia patients, which is highly correlated with thrombotic parameters.

22q11.2 Deletion Syndrome (22q11DS) is considered to be a promising cohort to explore biomarkers of schizophrenia risk based on a 30% probability of developing schizophrenia in adulthood. In this study, we investigated abnormalities in the microstructure of white matter in adolescents with 22q11DS and their specificity to prodromal symptoms of schizophrenia. Diffusion Magnetic Resonance Imaging (dMRI) data were acquired from 50 subjects with 22q11DS (9 with and 41 without prodromal psychotic symptoms), and 47 matched healthy controls (mean age 18 +/-2years). DMRI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated and compared between groups using the Tract Based Spatial Statistics (TBSS) method. Additionally, correlations between dMRI measures and scores on positive symptoms were performed. Reductions in MD, AD and RD (but not FA) were found in the corpus callosum (CC), left and right superior longitudinal fasciculus (SLF), and left and right corona radiata in the entire 22q11DS group. In addition, the 22q11DS subgroup with prodromal symptoms showed reductions in AD and MD, but no changes in RD when compared to the non-prodromal subgroup, in CC, right SLF, right corona radiata and right internal capsule. Finally, AD values in these tracts correlated with the scores on the psychosis subscale. Microstructural abnormalities in brain white matter are present in adolescent subjects with prodromal psychotic symptoms.

Spinal cord injury (SCI) is a severe disorder of the CNS leading to tissue damage and disability. Because it is critical to understand the pathological processes, it is important to find efficient ways to diagnose the severity of injured spinal cord tracts in situ from beginning up to a certain level of recovery following therapeutic interventions. In the current study, we set-up the criteria for diffusion tensor imaging (DTI) in order to capture changes of nerve fibre tracts in rat spinal cord compression injury. We tested four DTI parameters, such as fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity at the lesion site, in time course of 7weeks. Afterwards, we compared DTI data with histological results and locomotor outcomes to examine their consistency and capability of reflecting the lesion development in time. Our data confirm that DTI is avaluable in vivo imaging tool capable to distinguish damaged white matter tracts after mild SCI in rat. Fractional anisotropy showed decreased values for injury site, while the mean diffusivity had higher values, with increased both axial and radial diffusivity in comparison to control subjects. Thus, the combination of DTI parameters can reflect the severity of lesion in time and may correlate with histological evaluation of spared tissue, but not with locomotor recovery following mild injury associated with spontaneous recovery.