Diffusion Tensor Imaging Measures Research Articles

Brain functional magnetic resonance imaging in ICU patients who developed delirium

ObjectiveTo detect brain alterations in intensive care unit (ICU) patients who develop delirium using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) and to determine their predictive value.MethodsFifty-two patients who were admitted to the ICU of the Affiliated Hospital of Zunyi Medical University between June 2021 and June 2022 were enrolled. Fifteen patients who were diagnosed with delirium by the Intensive Care Delirium Screening Checklist (ICDSC) after MRI were selected as the delirium group, and 15 healthy volunteers who were examined during the same period served as the control group. Both groups underwent fMRI and DTI. Quantitative fMRI and DTI data were compared between the two groups to detect abnormal structural and functional brain damage. The relationships between MRI outliers and clinical indicators in the delirium group were also assessed.ResultsDemographic characteristics and imaging indicators before delirium were not correlated with ICDSC scores after delirium. Compared with the healthy control group, the delirium group had significantly lower regional homogeneity (ReHo) values in the left caudate nucleus and frontal lobe on fMRI. The amplitude of the low-frequency fluctuations (ALFF) values of the delirium group were significantly increased in the hippocampus but significantly decreased in the frontal lobe. Compared with the healthy control group, the delirium group showed reduced mean diffusivity (MD) values, mainly in the right cerebellum and right middle temporal gyrus; reduced radial diffusivity (RD) values, mainly in the anterior cerebellum and right middle temporal gyrus; reduced fractional anisotropy (FA) values, only in the corpus callosum; and reduced axial diffusivity (AD) values, mainly in the anterior cerebellar lobe, right middle temporal gyrus, and left middle frontal gyrus on DTI. The statistical thresholds for quantitative DTI measurements were p < 0.005 at the voxel level and a cluster size > 5.ConclusionAbnormal resting-state brain activity in the left superior frontal gyrus and structural changes in the frontal lobe, temporal lobe, corpus callosum, hippocampus, and cerebellum were observed in ICU patients who developed delirium during hospitalization. Early-brain fMRI and DTI examinations are recommended for the prediction of delirium according to unique quantitative indicators to facilitate early intervention for critically ill patients, reduce the length of hospital stay, and improve patient prognosis.

Essential Nutrients and White Matter Hyperintensities: A Two-Sample Mendelian Randomization Study.

Stroke and dementia have been linked to the appearance of white matter hyperintensities (WMHs). Meanwhile, diffusion tensor imaging (DTI) might capture the microstructural change in white matter early. Specific dietary interventions may help to reduce the risk of WMHs. However, research on the relationship between specific nutrients and white matter changes is still lacking. We aimed to investigate the causal effects of essential nutrients (amino acids, fatty acids, mineral elements, and vitamins) on WMHs and DTI measures, including fraction anisotropy (FA) and mean diffusivity (MD), by a Mendelian randomization analysis. We selected single nucleotide polymorphisms (SNPs) associated with each nutrient as instrumental variables to assess the causal effects of nutrient-related exposures on WMHs, FA, and MD. The outcome was from a recently published large-scale European Genome Wide Association Studies pooled dataset, including WMHs (N = 18,381), FA (N = 17,663), and MD (N = 17,467) data. We used the inverse variance weighting (IVW) method as the primary method, and sensitivity analyses were conducted using the simple median, weighted median, and MR-Egger methods. Genetically predicted serum calcium level was positively associated with WMHs risk, with an 8.1% increase in WMHs risk per standard deviation unit increase in calcium concentration (OR = 1.081, 95% CI = 1.006-1.161, p = 0.035). The plasma linoleic acid level was negatively associated with FA (OR = 0.776, 95% CI = 0.616-0.978, p = 0.032). Our study demonstrated that genetically predicted calcium was a potential risk factor for WMHs, and linoleic acid may be negatively associated with FA, providing evidence for interventions from the perspective of gene-environment interactions.

485 Investigating the Impact of Inflammation on White Matter Tracts using Diffusion Tensor Imaging that may Contribute to Motivational Deficits and Negative Symptoms in Patients with Schizophrenia

OBJECTIVES/GOALS: Previous research has linked inflammation to changes in brain reward circuitry and subsequent negative symptoms in patients with schizophrenia. This project aims to understand brain-immune interactions using diffusion tensor imaging (DTI) to investigate the impact of inflammatory markers on white matter (WM) tracts. METHODS/STUDY POPULATION: Patients with schizophrenia, ages 18 to 45, were recruited at Grady Hospital in Atlanta, GA. All subjects were stable outpatients and underwent extensive medical screening to rule out medical causes of acute inflammation. DTI data was collected from 39 participants on a 3-Tesla Siemens scanner. Blood was collected between 9-11AM for later assay of serum inflammatory markers. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS). A diffusion tensor imaging model will be fitted with the data to generate well-known diffusion tensor measures (fractional anisotropy and mean diffusivity). Linear regression will be used to analyze the relationship between DTI measures and inflammation (C-Reactive Protein, CRP), controlling for possible confounders. RESULTS/ANTICIPATED RESULTS: The hypothesis of this proposal is that decreased microstructural integrity in WM tracts between the nucleus accumbens (NAc) and insula will be associated with increased inflammation, which in turn are associated with increased negative symptoms. Negative symptoms include deficits in motivation/pleasure as well as diminished expressivity, and are strongly associated with poor functional outcomes. Based on previous data from this sample demonstrating relationships between CRP and negative symptoms as well as CRP and fMRI functional connectivity between the NAc and insula, we anticipate results that demonstrate similar relationships with WM microstructural integrity, such as functional anisotropy and mean diffusivity. DISCUSSION/SIGNIFICANCE: Given the lack of treatment options for negative symptoms, this research will provide key data to further our understanding of the potential role of inflammation on neural circuits that underlie these symptoms, including WM integrity. This research also has the potential to inform future anti-inflammatory therapies for patients with schizophrenia.

178 Brains on the Pitch: Investigating the Neurophysiological and Neurocognitive Effects of Repetitive Head Impacts in Adolescent Female Soccer Players During a Single Season

INTRODUCTION: Repetitive exposure to head impact in contact sports has raised concerns for potential long-term structural and functional neurologic effects. This relationship has been minimally explored in female athletes, with conflicting results arising from the limited reports on this topic. METHODS: Prospective cohort design with pre- and post-season assessments of neurocognitive function, transcranial magnetic stimulation (TMS), and diffusion tensor imaging (DTI). Neurocognitive battery evaluated processing speed, memory, and executive function domains via computerized (ImPACT) and paper-and-pencil testing. TMS assessments included motor evoked potential onset; interhemispheric conduction times; intercortical and intracortical inhibition. DTI measures included fractional anisotropy (FA) for white matter tracts of interest, including: posterior limb of internal capsule; cortical spinal tract; corpus callosum - selected for common involvement in traumatic brain injury within other studies. RESULTS: One player was officially diagnosed with concussion and was included in analysis. Neurocognitive performance was intact relative to same aged peers, and there were no significant differences over the season based on mean reliable change indices (-0.79-0.93). Paired t-test analysis indicated that the TMS measures were not significantly different between the two timepoints. Furthermore, DTI FA values and TMS measures were not notably different pre- versus postseason. CONCLUSIONS: In this cohort of high school female athletes, we did not observe significant anatomic, physiologic, or functional effects from repetitive head impacts. Our findings contradict previous studies that showed significant neurophysiologic and neurocognitive changes, even in the absence of clinically-observed concussion. Further research is needed to fully understand the long-term consequences of repetitive head impacts in female athletes and to develop effective strategies for mitigating potential risks.

Down-sampling in diffusion MRI: a bundle-specific DTI and NODDI study.

Multi-shell diffusion Magnetic Resonance Imaging (dMRI) data has been widely used to characterise white matter microstructure in several neurodegenerative diseases. The lack of standardised dMRI protocols often implies the acquisition of redundant measurements, resulting in prolonged acquisition times. In this study, we investigate the impact of the number of gradient directions on Diffusion Tensor Imaging (DTI) and on Neurite Orientation Dispersion and Density Imaging (NODDI) metrics. Data from 124 healthy controls collected in three different longitudinal studies were included. Using an in-house algorithm, we reduced the number of gradient directions in each data shell. We estimated DTI and NODDI measures on six white matter bundles clinically relevant for neurodegenerative diseases. Fractional Anisotropy (FA) measures on bundles where data were sampled at the 30% rate, showed a median L1 distance of up to 3.92% and a 95% CI of (1.74, 8.97)% when compared to those obtained at reference sampling. Mean Diffusivity (MD) reached up to 4.31% and a 95% CI of (1.60, 16.98)% on the same premises. At a sampling rate of 50%, we obtained a median of 3.90% and a 95% CI of (1.99, 16.65)% in FA, and 5.49% with a 95% CI of (2.14, 21.68)% in MD. The Intra-Cellular volume fraction (ICvf) median L1 distance was up to 2.83% with a 95% CI of (1.98, 4.82)% at a 30% sampling rate and 3.95% with a 95% CI of (2.39, 7.81)% at a 50% sampling rate. The volume difference of the reconstructed white matter at reference and 50% sampling reached a maximum of (2.09 ± 0.81)%. In conclusion, DTI and NODDI measures reported at reference sampling were comparable to those obtained when the number of dMRI volumes was reduced by up to 30%. Close to reference DTI and NODDI metrics were estimated with a significant reduction in acquisition time using three shells, respectively with: 4 directions at a b value of 700 s/mm2, 14 at 1000 s/mm2, and 32 at 2000 s/mm2. The study revealed aspects that can be important for large-scale clinical studies on bundle-specific diffusion MRI.

Unraveling the gut-brain connection: The association of microbiota-linked structural brain biomarkers with behavior and mental health.

The gut microbiota can influence human behavior. However, due to the massive multiple-testing problem, research into the relationship between microbiome ecosystems and the human brain faces drawbacks. This problem arises when attempting to correlate thousands of gut bacteria with thousands of brain voxels. We performed brain magnetic resonance imaging (MRI) scans on 133 participants and applied machine-learning algorithms (Ridge regressions) combined with permutation tests. Using this approach, we were able to correlate specific gut bacterial families with brain MRI signals, circumventing the difficulties of massive multiple testing while considering sex, age, and body mass index as confounding factors. The relative abundance (RA) of the Selenomonadaceae, Clostridiaceae, and Veillonellaceae families in the gut was associated with altered cerebellar, visual, and frontal T2-mapping and diffusion tensor imaging measures. Conversely, decreased relative abundance of the Eubacteriaceae family was also linked to T2-mapping values in the cerebellum. Significantly, the brain regions associated with the gut microbiome were also correlated with depressive symptoms and attentional deficits. Our analytical strategy offers a promising approach for identifying potential brain biomarkers influenced by gut microbiota. By gathering a deeper understanding of the microbiota-brain connection, we can gain insights into the underlying mechanisms and potentially develop targeted interventions to mitigate the detrimental effects of dysbiosis on brain function and mental health.

Interactions between overweight/obesity and alcohol dependence impact human brain white matter microstructure: evidence from DTI.

There is inconsistent evidence for an association of obesity with white matter microstructural alterations. Such inconsistent findings may be related to the cumulative effects of obesity and alcohol dependence. This study aimed to investigate the possible interactions between alcohol dependence and overweight/obesity on white matter microstructure in the human brain. A total of 60 inpatients with alcohol dependence during early abstinence (44 normal weight and 16 overweight/obese) and 65 controls (42 normal weight and 23 overweight/obese) were included. The diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and radial diffusivity (RD)] of the white matter microstructure were compared between groups. We observed significant interactive effects between alcohol dependence and overweight/obesity on DTI measures in several tracts. The DTI measures were not significantly different between the overweight/obese and normal-weight groups (although widespread trends of increased FA and decreased RD were observed) among controls. However, among the alcohol-dependent patients, the overweight/obese group had widespread reductions in FA and widespread increases in RD, most of which significantly differed from the normal-weight group; among those with overweight/obesity, the alcohol-dependent group had widespread reductions in FA and widespread increases in RD, most of which were significantly different from the control group. This study found significant interactive effects between overweight/obesity and alcohol dependence on white matter microstructure, indicating that these two controllable factors may synergistically impact white matter microstructure and disrupt structural connectivity in the human brain.

Neural and Cognitive Predictors of Stimulant Treatment Efficacy in Medication-Naïve ADHD Adults: A Pilot Diffusion Tensor Imaging Study

Objective: Stimulant medications are the main treatment for Attention Deficit Hyperactivity Disorder (ADHD), but overall treatment efficacy in adults has less than a 60% response rate. This study aimed to identify neural and cognitive markers predictive of longitudinal improvement in response to stimulant treatment in drug-naïve adults with ADHD. Method: We used diffusion tensor imaging (DTI) and executive function measures with 36 drug-naïve adult ADHD patients in a prospective study design. Results: Structural connectivity (measured by fractional anisotropy, FA) in striatal regions correlated with ADHD clinical symptom improvement following stimulant treatment (amphetamine or methylphenidate) in better medication responders. A significant positive correlation was also found between working memory performance and stimulant-related symptom improvement. Higher pre-treatment working memory scores correlated with greater response. Conclusion: These findings provide evidence of pre-treatment neural and behavioral markers predictive of longitudinal treatment response to stimulant medications in adults with ADHD.

Diffusion Tensor Imaging for Characterizing Changes in Triple-Negative Breast Cancer During Neoadjuvant Systemic Therapy.

Assessment of treatment response in triple-negative breast cancer (TNBC) may guide individualized care for improved patient outcomes. Diffusion tensor imaging (DTI) measures tissue anisotropy and could be useful for characterizing changes in the tumors and adjacent fibroglandular tissue (FGT) of TNBC patients undergoing neoadjuvant systemic treatment (NAST). To evaluate the potential of DTI parameters for prediction of treatment response in TNBC patients undergoing NAST. Prospective. Eighty-six women (average age: 51 ± 11 years) with biopsy-proven clinical stage I-III TNBC who underwent NAST followed by definitive surgery. 47% of patients (40/86) had pathologic complete response (pCR). 3.0 T/reduced field of view single-shot echo-planar DTI sequence. Three MRI scans were acquired longitudinally (pre-treatment, after 2 cycles of NAST, and after 4 cycles of NAST). Eleven histogram features were extracted from DTI parameter maps of tumors, a peritumoral region (PTR), and FGT in the ipsilateral breast. DTI parameters included apparent diffusion coefficients and relative diffusion anisotropies. pCR status was determined at surgery. Longitudinal changes of DTI features were tested for discrimination of pCR using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC). A P value <0.05 was considered statistically significant. 47% of patients (40/86) had pCR. DTI parameters assessed after 2 and 4 cycles of NAST were significantly different between pCR and non-pCR patients when compared between tumors, PTRs, and FGTs. The median surface/average anisotropy of the PTR, measured after 2 and 4 cycles of NAST, increased in pCR patients and decreased in non-pCR patients (AUC: 0.78; 0.027 ± 0.043 vs. -0.017 ± 0.042 mm2 /s). Quantitative DTI features from breast tumors and the peritumoral tissue may be useful for predicting the response to NAST in TNBC. 1 TECHNICAL EFFICACY: Stage 4.

Diffusion tensor imaging: survival analysis prediction in breast cancer patients.

We aimed to explore the performance of diffusion-tensor imaging (DTI) and apparent diffusion coefficient (ADC) parameters in evaluating disease-free survival (DFS) and overall survival (OS) in patients with invasive breast cancer. Atotal of 49women with invasive breast cancer who were diagnosed between 2017 and 2022 were included. All patients underwent breast magnetic resonance imaging (MRI) with DTI and diffusion-weighted imaging (DWI) features, with examiners blinded to the clinical data. Volume anisotropy (VA), fractional anisotropy (FA), and ADC values were measured to assess intratumoral measured heterogeneity. Correlations and differences in diffusion metrics according to OS and DFS status of the cases were analyzed. The discriminative ability of the quantitative findings was assessed by receiver operating characteristic (ROC) curve analyses and validated in the independent cohort. We evaluated patients with metastases (n = 13, 36.5%) and those without metastases (n = 36, 73.5%). Differences in the ADC, FA, and VA values were observed. The results of Cox regression survival analysis for all the patients included in the survival analysis revealed that DTI metrics contributed to the prediction of overall survival (OS) in the emerging models (p < 0.05). Both FA and VA were associated with OS (p = 0.037 and p = 0.038, respectively). However, ADC was not associated with OS (p = 0.177) or DFS (p = 0.252). To the best of our knowledge, this is the first study to assess the prognostic value of DTI-MRI in breast cancer with statistical survival analysis techniques. We believe that DTI measurements can be used as abiomarker for OS analysis in breast cancer given the available data.

Folate receptor α deficiency - Myelin-sensitive MRI as a reliable biomarker to monitor the efficacy and long-term outcome of a new therapeutic approach.

Cerebral folate transport deficiency, caused by a genetic defect in folate receptor α, is a devastating neurometabolic disorder that, if untreated, leads to epileptic encephalopathy, psychomotor decline and hypomyelination. Currently, there are limited data on effective dosage and duration of treatment, though early diagnosis and therapy with folinic acid appears critical. The aim of this long-term study was to identify new therapeutic approaches and novel biomarkers for assessing efficacy, focusing on myelin-sensitive MRI. Clinical, biochemical, structural and quantitative MRI parameters of seven patients with genetically confirmed folate receptor α deficiency were acquired over 13 years. Multimodal MRI approaches comprised MR-spectroscopy (MRS), magnetization transfer (MTI) and diffusion tensor imaging (DTI) sequences. Patients started oral treatment immediately following diagnosis or in an interval of up to 2.5 years. Escalation to intravenous and intrathecal administration was performed in the absence of effects. Five patients improved, one with a presymptomatic start of therapy remained symptom-free, and one with inconsistent treatment deteriorated. While CSF 5-methyltetrahydrofolate and MRS parameters normalized immediately after therapy initiation, myelin-sensitive MTI and DTI measures correlated with gradual clinical improvement and ongoing myelination under therapy. Early initiation of treatment at sufficient doses, considering early intrathecal applications, is critical for favorable outcome. The majority of patients showed clinical improvements that correlated best with MTI parameters, allowing individualized monitoring of myelination recovery. Presymptomatic therapy seems to ensure normal development and warrants newborn screening. Furthermore, the quantitative parameters of myelin-sensitive MRI for therapy assessments can now be used for hypomyelination disorders in general.

White matter microstructure of children with sensory over-responsivity is associated with affective behavior.

Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging such as diffusion MRI (dMRI). Since SOR involves hypersensitivity to external stimuli, we test the hypothesis that children with SOR require compensatory neuroplasticity in the form of superior WM microstructural integrity to protect against internalizing behavior, leaving those with impaired WM microstructure vulnerable to somatization and depression. Children ages 8-12years old with neurodevelopmental concerns were assessed for SOR using a comprehensive structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment, and underwent 3 Tesla MRI with multishell multiband dMRI. Tract-based spatial statistics was used to measure diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics from global WM and nineteen selected WM tracts. Correlations of DTI and NODDI measures with measures of somatization and emotional disturbance from the Behavioral Assessment System for Children, 3rd edition (BASC-3), were computed in the SOR group and in matched children with neurodevelopmental concerns but not SOR. Global WM fractional anisotropy (FA) is negatively correlated with somatization and with emotional disturbance in the SOR group but not the non-SOR group. Also observed in children with SOR are positive correlations of radial diffusivity (RD) and free water fraction (FISO) with somatization and, in most cases, emotional disturbance. These effects are significant in boys with SOR, whereas the study is underpowered for girls. The most affected white matter are medial lemniscus and internal capsule sensory tracts, although effects of SOR are observed in many cerebral, cerebellar, and brainstem tracts. White matter microstructure is related to affective behavior in children with SOR.

Integrated Diffusion Tensor Imaging and Renal Parenchymal Volume for Early Detection and Grading of Split Renal Functional Impairment in Lupus Nephritis

To investigate the effectiveness of combining split diffusion tensor imaging (DTI) measurements with split renal parenchymal volume (RPV) for assessing split renal functional impairment in patients with lupus nephritis (LN). Seventy-four participants [48 LN patients and 26 healthy volunteers (HV)] were included in the study. All participant underwent conventional MR and DTI (b = 0, 400, and 600s/mm2) examinations using a 3.0T MRI scanner to determine the split renal DTI measurements and split RPV. In LN patients, renography glomerular filtration rate (rGFR) was measured using 99mTc-DTPA scintigraphy based on Gates' method, serving as the reference standard to categorize all split kidneys of LN patients into LN with mild impairment (LNm, n=65 kidneys) and LN with moderate to severe (LNms, n=31 kidneys) groups according to the threshold of 30ml/min in spilt rGFR. All statistical analyses were performed using SPSS 25.0 and MedCalc 20.0 software packages. Only split medullary fractional anisotropy (FA) and the product of split medullary FA and RPV could distinguish pairwise subgroups among the HV and each LN subgroup (all p<0.05). ROC curve analysis demonstrated that split medullary FA (AUC=0.866) significantly outperformed other parameters in differentiating HV from LNm groups, while the product of split medullary FA and split RPV was superior in distinguishing LNm and LNms groups (AUC=0.793) than other parameters. The combination of split medullary FA and split RPV showed best correlation with split rGFR (r=0.534, p<0.001). Split medullary FA, and its combination with split RPV, are valuable biomarkers for detecting early functional changes in renal alterations and predicting disease progression in patients with LN.

Structural volumetric and Periodic Table DTI patterns in Complex Normal Pressure Hydrocephalus-Toward the principles of a translational taxonomy.

We previously proposed a novel taxonomic framework to describe the diffusion tensor imaging (DTI) profiles of white matter tracts by their diffusivity and neural properties. We have shown the relevance of this strategy toward interpreting brain tissue signatures in Classic Normal Pressure Hydrocephalus vs. comparator cohorts of mild traumatic brain injury and Alzheimer's disease. In this iteration of the Periodic Table of DTI Elements, we examined patterns of tissue distortion in Complex NPH (CoNPH) and validated the methodology against an open-access dataset of healthy subjects, to expand its accessibility to a larger community. DTI measures for 12 patients with CoNPH with multiple comorbidities and 45 cognitively normal controls from the ADNI database were derived using the image processing pipeline on the brainlife.io open cloud computing platform. Using the Periodic Table algorithm, DTI profiles for CoNPH vs. controls were mapped according to injury patterns. Structural volumes in most structures tested were significantly lower and the lateral ventricles higher in CoNPH vs. controls. In CoNPH, significantly lower fractional anisotropy (FA) and higher mean, axial, and radial diffusivities (MD, L1, and L2 and 3, respectively) were observed in white matter related to the lateral ventricles. Most diffusivity measures across supratentorial and infratentorial structures were significantly higher in CoNPH, with the largest differences in the cerebellum cortex. In subcortical deep gray matter structures, CoNPH and controls differed most significantly in the hippocampus, with the CoNPH group having a significantly lower FA and higher MD, L1, and L2 and 3. Cerebral and cerebellar white matter demonstrated more potential reversibility of injury compared to cerebral and cerebellar cortices. The findings of widespread and significant reductions in subcortical deep gray matter structures, in comparison to healthy controls, support the hypothesis that Complex NPH cohorts retain imaging features associated with Classic NPH. The use of the algorithm of the Periodic Table allowed for greater consistency in the interpretation of DTI results by focusing on patterns of injury rather than an over-reliance on the interrogation of individual measures by statistical significance alone. Our aim is to provide a prototype that could be refined for an approach toward the concept of a "translational taxonomy."

Association of quantitative diffusion tensor imaging measures with time to return to sport and reinjury incidence following acute hamstring strain injury

Hamstring strain injuries (HSI) are a common occurrence in athletics and complicated by limited prognostic indicators and high rates of reinjury. Assessment of injury characteristics at the time of injury (TOI) may be used to manage athlete expectations for time to return to sport (RTS) and mitigate reinjury risk. Magnetic resonance imaging (MRI) is routinely used in soft tissue injury management, but its prognostic value for HSI is widely debated. Recent advancements in musculoskeletal MRI, such as diffusion tensor imaging (DTI), have allowed for quantitative measures of muscle microstructure assessment. The purpose of this study was to determine the association of TOI MRI-based measures, including the British Athletic Muscle Injury Classification (BAMIC) system, edema volume, and DTI metrics, with time to RTS and reinjury incidence. Negative binomial regressions and generalized estimating equations were used to determine relationships between imaging measures and time to RTS and reinjury, respectively. Twenty-six index injuries were observed, with five recorded reinjuries. A significant association was not detected between BAMIC score and edema volume at TOI with days to RTS (p-values ≥ 0.15) or reinjury (p-values ≥ 0.13). Similarly, a significant association between DTI metrics and days to RTS was not detected (p-values ≥ 0.11). Although diffusivity metrics are expected to increase following injury, decreased values were observed in those who reinjured (mean diffusivity, p = 0.016; radial diffusivity, p = 0.02; principal effective diffusivity eigenvalues, p-values = 0.007–0.057). Additional work to further understand the directional relationship observed between DTI metrics and reinjury status and the influence of external factors is warranted.

Circulating cytotoxic immune cell composition, activation status and toxins expression associate with white matter microstructure in bipolar disorder

Patients with bipolar disorder (BD) show higher immuno-inflammatory setpoints, with in vivo alterations in white matter (WM) microstructure and post-mortem infiltration of T cells in the brain. Cytotoxic CD8+ T cells can enter and damage the brain in inflammatory disorders, but little is known in BD. Our study aimed to investigate the relationship between cytotoxic T cells and WM alterations in BD. In a sample of 83 inpatients with BD in an active phase of illness (68 depressive, 15 manic), we performed flow cytometry immunophenotyping to investigate frequencies, activation status, and expression of cytotoxic markers in CD8+ and tested for their association with diffusion tensor imaging (DTI) measures of WM microstructure. Frequencies of naïve and activated CD8+ cell populations expressing Perforin, or both Perforin and Granzyme, negatively associated with WM microstructure. CD8+ Naïve cells negative for Granzyme and Perforin positively associates with indexes of WM integrity, while the frequency of CD8+ memory cells negatively associates with index of WM microstructure, irrespective of toxins expression. The resulting associations involve measures representative of orientational coherence and myelination of the fibers (FA and RD), suggesting disrupted oligodendrocyte-mediated myelination. These findings seems to support the hypothesis that immunosenescence (less naïve, more memory T cells) can detrimentally influence WM microstructure in BD and that peripheral CD8+ T cells may participate in inducing an immune-related WM damage in BD mediated by killer proteins.

Changes in lumbar muscle diffusion tensor indices with age.

To investigate differences in diffusion tensor imaging (DTI) parameters and proton density fat fraction (PDFF) in the spinal muscles of younger and older adult males. Twelve younger (19-30 years) and 12 older (61-81years) healthy, physically active male participants underwent T1W, T2W, Dixon and DTI of the lumbar spine. The eigenvalues (λ1, λ2, and λ3), fractional anisotropy (FA), and mean diffusivity (MD) from the DTI together with the PDFF were determined in the multifidus, medial and lateral erector spinae (ESmed, ESlat), and quadratus lumborum (QL) muscles. A two-way ANOVA was used to investigate differences with age and muscle and t-tests for differences in individual muscles with age. The ANOVA gave significant differences with age for all DTI parameters and the PDFF (P < .01) and with muscle (P < .01) for all DTI parameters except for λ1 and for the PDFF. The mean of the eigenvalues and MD were lower and the FA higher in the older age group with differences reaching statistical significance for all DTI measures for ESlat and QL (P < .01) but only in ESmed for λ3 and MD (P < .05). Differences in DTI parameters of muscle with age result from changes in both in the intra- and extra-cellular space and cannot be uniquely explained in terms of fibre length and diameter. Previous studies looking at age have used small groups with uneven age spacing. Our study uses two well defined and separated age groups.

Age-associated alterations in thalamocortical structural connectivity in youths with a psychosis-spectrum disorder

Psychotic symptoms typically emerge in adolescence. Age-associated thalamocortical connectivity differences in psychosis remain unclear. We analyzed diffusion-weighted imaging data from 1254 participants 8–23 years old (typically developing (TD):N = 626, psychosis-spectrum (PS): N = 329, other psychopathology (OP): N = 299) from the Philadelphia Neurodevelopmental Cohort. We modeled thalamocortical tracts using deterministic fiber tractography, extracted Q-Space Diffeomorphic Reconstruction (QSDR) and diffusion tensor imaging (DTI) measures, and then used generalized additive models to determine group and age-associated thalamocortical connectivity differences. Compared to other groups, PS exhibited thalamocortical reductions in QSDR global fractional anisotropy (GFA, p-values range = 3.0 × 10–6–0.05) and DTI fractional anisotropy (FA, p-values range = 4.2 × 10–4–0.03). Compared to TD, PS exhibited shallower thalamus-prefrontal age-associated increases in GFA and FA during mid-childhood, but steeper age-associated increases during adolescence. TD and OP exhibited decreases in thalamus-frontal mean and radial diffusivities during adolescence; PS did not. Altered developmental trajectories of thalamocortical connectivity may contribute to the disruptions observed in adults with psychosis.

Neurite‐based white matter alterations in MAPT mutation carriers: A multi‐shell diffusion MRI study in the ALLFTD consortium

AbstractBackgroundWe aimed to assess axonal integrity in MAPT mutation carriers and early white matter (WM) neurodegeneration in asymptomatic carriers using traditional diffusion tensor imaging (DTI) measurements, i.e., fractional anisotropy (FA) and mean diffusivity (MD), and neurite orientation dispersion and density imaging (NODDI).MethodWe included available multi‐shell diffusion MRI data from 21 MAPT mutation carriers (16 asymptomatic; 5 symptomatic) and 31 non‐carrier family members as controls from the ALLFTD consortium. We used linear mixed‐effect models to assess WM abnormalities measured with FA and MD, neurite density index (NDI) and orientation dispersion index (ODI), combined across hemispheres. Separate models were conducted in all MAPT mutation carriers relative to controls while accounting for relatedness and age, then in symptomatic and asymptomatic carriers relative to controls. ComBat was used to harmonize data across sites.ResultIn models contrasting all MAPT carriers versus controls, WM alterations involved the cingulum bundle (FA, ODI), fronto‐temporal, entorhinal (FA, MD, NDI), and the inferior temporal WM (FA) after correcting for multiple comparisons (Fig. 1). In models contrasting symptomatic and asymptomatic MAPT carriers versus controls, symptomatic carriers had widespread involvement of the fronto‐temporal WM including the cingulum (FA, ODI), entorhinal (MD, FA, NDI), amygdala (MD, NDI) and inferior temporal (FA) areas after correcting for multiple comparisons. Asymptomatic carriers showed higher entorhinal MD and lower inferior temporal and cingulum FA relative to controls, and a more widespread pattern of higher ODI involved the medial temporal, superior temporal and occipital WM as well as long association and projection fibers including the internal capsule, cingulate bundle and fronto‐occipital fasciculi, although they were not statistically significant after correction for multiple comparisons.ConclusionTraditional DTI and novel NODDI measurements revealed some extent of overlap as well as divergences in patterns of WM abnormalities, indicating axonal loss is a feature of neurodegeneration in MAPT mutation carriers. Our results suggest that traditional DTI and novel NODDI measurements may have different sensitivities to WM alterations in MAPT mutation carriers, and that axon‐based metrics, particularly ODI measurements, may be more sensitive to the early WM involvement during the asymptomatic stage of the disease.

Brain Structure and Cognitive Dysfunction in Myotonic Dystrophy Type 2 (BraCE‐DM2)

AbstractBackgroundMyotonic dystrophy type 2 (DM2) is a pleiotropic multisystemic disease. Although progressive muscle weakness is the main symptom in DM2, almost two‐third of the patients report cognitive deficits as one of the most disabling symptoms. Emerging evidence has identified tau mis‐splicing and tangle pathology in DM2, which has prompted interest in elucidating the role of tau in DM2‐related cognitive impairment. Previous studies suggest that cerebral white matter (WM) is primarily affected in DM2. However, quantitative brain imaging studies incorporate with cognitive measures are extremely limited.Method3T brain MRIs were acquired in 10 adults with DM2 and 10 gender and age‐matched controls. Brain morphometry and WM integrity were assessed using T1‐MPRAGE and diffusion tensor imaging (DTI) sequences. DTI scalars, including fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and median diffusivity (MD) were compared between groups. A comprehensive battery of cognitive and behavioral measures was performed and correlated with MRI measures (Spearman’s Correlation).ResultOf 20 participants (60% female), mean age (62.2 vs. 62.6 years) and education (16.4 vs. 17.5 years) were similar between the two groups. Compared to controls, the DM2 group showed a significant reduction in global measures of cerebral gray matter (GM) volume in both cortex and deep gray structures (mean difference, ‐0.03; p&lt;0.01), but not the WM volume. Widespread abnormalities in DTI measures (lower FA, higher RD) were among the most robust findings in DM2 (mean differences of FA, 0.04; p&lt;0.01 and RD, 0.00004; p&lt;0.01), indicating that the pathology is within WM microstructures. Overall, the DM2 group scored lower than controls in all cognitive domains, particularly executive function (mean difference, ‐12.5; p = 0.04). We found a strong correlation between cerebral FA and a test of executive function (rho = 0.71, p = 0.02). Cerebral FA also showed a moderate correlation with processing speed (rho = 0.50) and apathy evaluation scale (rho = ‐0.43).ConclusionOur pilot data demonstrate robust differences of brain structure, explicitly measures of WM integrity and cerebral GM volume between the DM2 group vs. controls. The strong correlation between cerebral FA and executive function also supports the notion that WM integrity plays an important role in cognitive dysfunction in DM2.