Associations between psychosocial work environment factors and first-time and recurrent treatment for depression: a prospective cohort study of 24,226 employees.

AIMS: Adverse factors in the psychosocial work environment are associated with the onset of depression among those without a personal history of depression. However, the evidence is sparse regarding whether adverse work factors can also play a role in depression recurrence. This study aimed to prospectively examine whether factors in the psychosocial work environment are associated with first-time and recurrent treatment for depression. METHODS: The study included 24,226 participants from the Danish Well-being in Hospital Employees study. We measured ten individual psychosocial work factors and three theoretical constructs (effort-reward imbalance, job strain and workplace social capital). We ascertained treatment for depression through registrations of hospital contacts for depression (International Statistical Classification of Diseases and Related Health Problems version 10 [ICD-10]: F32 and F33) and redeemed prescriptions of antidepressant medication (Anatomical Therapeutic Chemical [ATC]: N06A) in Danish national registries. We estimated the associations between work factors and treatment for depression for up to 2 years after baseline among those without (first-time treatment) and with (recurrent treatment) a personal history of treatment for depression before baseline. We excluded participants registered with treatment within 6 months before baseline. In supplementary analyses, we extended this washout period to up to 2 years. We applied logistic regression analyses with adjustment for confounding. RESULTS: Among 21,156 (87%) participants without a history of treatment for depression, 350 (1.7%) had first-time treatment during follow-up. Among the 3070 (13%) participants with treatment history, 353 (11%) had recurrent treatment during follow-up. Those with a history of depression generally reported a more adverse work environment than those without such a history. Baseline exposure to bullying (odds ratio [OR] = 1.72, 95% confidence interval [95% CI]: 1.30-2.32), and to some extent also low influence on work schedule (OR = 1.27, 95% CI: 0.97-1.66) and job strain (OR = 1.24, 95% CI: 0.97-1.57), was associated with first-time treatment for depression during follow-up. Baseline exposure to bullying (OR = 1.40, 95% CI: 1.04-1.88), lack of collaboration (OR = 1.31, 95% CI: 1.03-1.67) and low job control (OR = 1.27, 95% CI: 1.00-1.62) were associated with recurrent treatment for depression during follow-up. However, most work factors were not associated with treatment for depression. Using a 2-year washout period resulted in similar or stronger associations. CONCLUSIONS: Depression constitutes a substantial morbidity burden in the working-age population. Specific adverse working conditions were associated with first-time and recurrent treatment for depression and improving these may contribute to reducing the onset and recurrence of depression.

Occupational risk of COVID-19 in foreign-born employees in Denmark.

BACKGROUND: Foreign-born workers in high-income countries experience higher rates of COVID-19 but the causes are only partially known. AIMS: To examine if the occupational risk of COVID-19 in foreign-born workers deviates from the risk in native-born employees in Denmark. METHODS: Within a registry-based cohort of all residents employed in Denmark (n = 2 451 542), we identified four-digit DISCO-08 occupations associated with an increased incidence of COVID-19-related hospital admission during 2020-21 (at-risk occupations). The sex-specific prevalence of at-risk employment in foreign born was compared with the prevalence in native born. Moreover, we examined if the country of birth modified the risk of a positive SARS-CoV-2 polymerase chain reaction (PCR) test and COVID-19-related hospital admission in at-risk occupations. RESULTS: Workers born in low-income countries and male workers from Eastern Europe more often worked in at-risk occupations (relative risks between 1.16 [95% confidence interval {CI} 1.14-1.17] and 1.87 [95% CI 1.82-1.90]). Being foreign-born modified the adjusted risk of PCR test positivity (test for interaction P < 0.0001), primarily because of higher risk in at-risk occupations among men born in Eastern European countries (incidence rate ratio [IRR] 2.39 [95% CI 2.09-2.72] versus IRR 1.19 [95% CI 1.14-1.23] in native-born men). For COVID-19-related hospital admission, no overall interaction was seen, and in women, country of birth did not consistently modify the occupational risk. CONCLUSIONS: Workplace viral transmission may contribute to an excess risk of COVID-19 in male workers born in Eastern Europe, but most foreign-born employees in at-risk occupations seem not to be at higher occupational risk than native born.

Quantitative Diffusion and Spectroscopic Neuroimaging Combined with a Novel Early-Developmental Assessment Improves Models for 1-Year Developmental Outcomes.

BACKGROUND AND PURPOSE: Preterm infants are at risk for overt and silent CNS injury, with developmental consequences that are difficult to predict. The novel Specific Test of Early Infant Motor Performance, administered in preterm infants at term age, is indicative of later developmental gross motor and cognitive scores at 12 months. Here, we assessed whether functional performance on this early assessment correlates with CNS integrity via MR spectroscopy or diffusional kurtosis imaging and whether these quantitative neuroimaging methods improve predictions for future 12-month developmental scores. MATERIALS AND METHODS: MR spectroscopy and quantitative diffusion MR imaging data were acquired in preterm infants (n = 16) at term. Testing was performed at term and 3 months using the Specific Test of Early Infant Motor Performance and the Bayley Scales of Infant and Toddler Development, Third Edition, at 12 months. We modeled the relationship of MR spectroscopy and diffusion MR imaging data with both test scores via multiple linear regression. RESULTS: MR spectroscopy NAA ratios at a TE of 270 ms in the frontal WM and basal ganglia and kurtosis metrics in major WM tracts correlated strongly with total Specific Test of Early Infant Motor Performance scores. The addition of MR spectroscopy and diffusion separately improved the functional predictions of 12-month outcomes. CONCLUSIONS: Microstructural integrity of the major WM tracts and metabolism in the basal ganglia and frontal WM strongly correlate with early developmental performance, suggesting that the Specific Test of Early Infant Motor Performance reflects CNS integrity after preterm birth. This study demonstrates that combining quantitative neuroimaging and early functional movement improves the prediction of 12-month outcomes in premature infants.

First Accurate Normalization of the ß-delayed α Decay of

The ^{12}C(α,γ)^{16}O reaction plays a central role in astrophysics, but its cross section at energies relevant for astrophysical applications is only poorly constrained by laboratory data. The reduced α width, γ_{11}, of the bound 1^{-} level in ^{16}O is particularly important to determine the cross section. The magnitude of γ_{11} is determined via sub-Coulomb α-transfer reactions or the ß-delayed α decay of ^{16}N, but the latter approach is presently hampered by the lack of sufficiently precise data on the ß-decay branching ratios. Here we report improved branching ratios for the bound 1^{-} level [b_{ß,11}=(5.02±0.10)×10^{-2}] and for ß-delayed α emission [b_{ßα}=(1.59±0.06)×10^{-5}]. Our value for b_{ßα} is 33% larger than previously held, leading to a substantial increase in γ_{11}. Our revised value for γ_{11} is in good agreement with the value obtained in α-transfer studies and the weighted average of the two gives a robust and precise determination of γ_{11}, which provides significantly improved constraints on the ^{12}C(α,γ) cross section in the energy range relevant to hydrostatic He burning.

Diffusional Kurtosis Imaging of the Corticospinal Tract in Multiple Sclerosis: Association with Neurologic Disability.

BACKGROUND AND PURPOSE: Multiple sclerosis is an autoimmune disorder resulting in progressive neurologic disability. Our aim was to evaluate the associations between diffusional kurtosis imaging-derived metrics for the corticospinal tract and disability in multiple sclerosis. MATERIALS AND METHODS: Forty patients with MS underwent brain MR imaging including diffusional kurtosis imaging. After we masked out T2 hyperintense lesions, the fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity, mean kurtosis, radial kurtosis, and axial kurtosis were estimated for the corticospinal tract. Disability was quantified by using the Expanded Disability Status Scale at the time of MR imaging and 12 months post-MR imaging. The Pearson correlation coefficient and linear regression analyses were conducted to evaluate the associations between diffusion metrics and disability. RESULTS: Significant correlations were found between the Expanded Disability Status Scale scores during the baseline visit and age (r = 0.47), T2 lesion volume (r = 0.38), corticospinal tract mean diffusivity (r = 0.41), radial diffusivity (r = 0.41), axial diffusivity (r = 0.34), fractional anisotropy (r = -0.36), and radial kurtosis (r = -0.42). Significant correlations were also found between the Expanded Disability Status Scale scores at 12-month follow-up and age (r = 0.38), mean diffusivity (r = 0.45), radial diffusivity (r = 0.41), axial diffusivity (r = 0.45), mean kurtosis (r = -0.42), radial kurtosis (r = -0.56), and axial kurtosis (r = -0.36). Linear regression analyses demonstrated significant associations among radial kurtosis, age, and Expanded Disability Status Scale score during the baseline visit, while radial kurtosis was the only variable associated with Expanded Disability Status Scale score for the 12-month follow-up. CONCLUSIONS: Radial kurtosis of the corticospinal tract may have an association with neurologic disability in MS.

Diffusional Kurtosis Imaging and Motor Outcome in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Motor impairment is the most common deficit after stroke. Our aim was to evaluate whether diffusional kurtosis imaging can detect corticospinal tract microstructural changes in the acute phase for patients with first-ever ischemic stroke and motor impairment and to assess the correlations between diffusional kurtosis imaging-derived diffusion metrics for the corticospinal tract and motor impairment 3 months poststroke. MATERIALS AND METHODS: We evaluated 17 patients with stroke who underwent brain MR imaging including diffusional kurtosis imaging within 4 days after the onset of symptoms. Neurologic evaluation included the Fugl-Meyer Upper Extremity Motor scale in the acute phase and 3 months poststroke. For the corticospinal tract in the lesioned and contralateral hemispheres, we estimated with diffusional kurtosis imaging both pure diffusion metrics, such as the mean diffusivity and mean kurtosis, and model-dependent quantities, such as the axonal water fraction. We evaluated the correlations between corticospinal tract diffusion metrics and the Fugl-Meyer Upper Extremity Motor scale at 3 months. RESULTS: Among all the diffusion metrics, the largest percentage signal changes of the lesioned hemisphere corticospinal tract were observed with axial kurtosis, with an average 12% increase compared with the contralateral corticospinal tract. The strongest associations between the 3-month Fugl-Meyer Upper Extremity Motor scale score and diffusion metrics were found for the lesioned/contralateral hemisphere corticospinal tract mean kurtosis (ρ = -0.85) and axial kurtosis (ρ = -0.78) ratios. CONCLUSIONS: This study was designed to be one of hypothesis generation. Diffusion metrics related to kurtosis were found to be more sensitive than conventional diffusivity metrics to early poststroke corticospinal tract microstructural changes and may have potential value in the prediction of motor impairment at 3 months.

Solute Partitioning in Micelles: Combining Molecular Dynamics Simulations, COSMOmic, and Experiments.

The partition equilibria of solutes between micelles and an aqueous phase is a key factor in many applications. Depending on the task, many micelle-solute combinations are possible. Therefore, theoretical methods to predict the partition behavior in micellar systems are needed. Here, two predictive methods are evaluated and compared. First, it is shown how molecular dynamics simulations (MD) with the umbrella sampling method can be used to calculate free energy profiles in micellar systems. The second applied method is an extension of the COSMO-RS theory to anisotropic systems termed COSMOmic. Both methods are compared by means of free energy profiles and experimental micelle/water partition coefficients. A particular focus is on the partitioning of ionized solutes. As experimental data for partitioning in micelles especially for charged solutes is rare, partition coefficients were also determined experimentally. To get a general understanding of micelles examples of all micelle classes (classified by headgroup charge) are studied: nonionic Triton X-114 (TX114), zwitterionic miltefosine (HePC), anionic sodium dodecyl sulfate (SDS), and cationic cetyltrimethylammonium bromid (CTAB). The free energy profiles of neutral solutes obtained from MD simulations and COSMOmic are in an overall good agreement, and partition coefficients from both methods are in good agreement with experimental data. Depending on the system, the results for charged solutes show some deviations between the methods and experimental data.

Simultaneous High-Throughput Conformational and Colloidal Stability Screening Using a Fluorescent Molecular Rotor Dye, 4-(4-(Dimethylamino)styryl)-N-Methylpyridinium Iodide (DASPMI).

Technologies to improve the throughput for screening protein formulations are continuously evolving. The purpose of this article is to highlight novel applications of a molecular rotor dye, 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (DASPMI) in screening for the conformational stability, colloidal stability, and subtle pretransition dynamics of protein structures during early formulation development. The measurement of the apparent unfolding temperature (Tm) for a monoclonal antibody in the presence of Tween 80 was conducted and data were compared to the results of differential scanning calorimetry (DSC) measurements. Additionally, measuring the fluorescence intensity of DASPMI as a function of protein concentration shows consistent correlation to the diffusion interaction parameter (kD) for two distinct monoclonal antibody formulations measured by DLS. Lastly, due to the sensitivity of the molecular rotor dye to changes in microviscosity (ηmicro), subtle pretransition dynamics were discernable for two monoclonal antibody formulations that correlate with findings by red-edge excitation shift (REES) experiments. This novel application of molecular rotor dyes offers a valuable and promising approach for streamlining the early formulation development process due to low material consumption and rapid analysis time in a 96-well plate format.

Mapping the Orientation of White Matter Fiber Bundles: A Comparative Study of Diffusion Tensor Imaging, Diffusional Kurtosis Imaging, and Diffusion Spectrum Imaging.

BACKGROUND AND PURPOSE: White matter fiber tractography relies on fiber bundle orientation estimates from diffusion MR imaging. However, clinically feasible techniques such as DTI and diffusional kurtosis imaging use assumptions, which may introduce error into in vivo orientation estimates. In this study, fiber bundle orientations from DTI and diffusional kurtosis imaging are compared with diffusion spectrum imaging as a criterion standard to assess the performance of each technique. MATERIALS AND METHODS: For each subject, full DTI, diffusional kurtosis imaging, and diffusion spectrum imaging datasets were acquired during 2 independent sessions, and fiber bundle orientations were estimated by using the specific theoretic assumptions of each technique. Angular variability and angular error measures were assessed by comparing the orientation estimates. Tractography generated with each of the 3 reconstructions was also examined and contrasted. RESULTS: Orientation estimates from all 3 techniques had comparable angular reproducibility, but diffusional kurtosis imaging decreased angular error throughout the white matter compared with DTI. Diffusion spectrum imaging and diffusional kurtosis imaging enabled the detection of crossing-fiber bundles, which had pronounced effects on tractography relative to DTI. Diffusion spectrum imaging had the highest sensitivity for detecting crossing fibers; however, the diffusion spectrum imaging and diffusional kurtosis imaging tracts were qualitatively similar. CONCLUSIONS: Fiber bundle orientation estimates from diffusional kurtosis imaging have less systematic error than those from DTI, which can noticeably affect tractography. Moreover, tractography obtained with diffusional kurtosis imaging is qualitatively comparable with that of diffusion spectrum imaging. Because diffusional kurtosis imaging has a shorter typical scan time than diffusion spectrum imaging, diffusional kurtosis imaging is potentially more suitable for a variety of clinical and research applications.

Non-Gaussian diffusion MRI of gray matter is associated with cognitive impairment in multiple sclerosis.

BACKGROUND: Non-Gaussian diffusion imaging by using diffusional kurtosis imaging (DKI) allows assessment of isotropic tissue as of gray matter (GM), an important limitation of diffusion tensor imaging (DTI). OBJECTIVE: In this study, we describe DKI and DTI metrics of GM in multiple sclerosis (MS) patients and their association with cognitive deficits. METHODS: Thirty-four patients with relapsing-remitting MS and 17 controls underwent MRI on a 3T scanner including a sequence for DKI with 30 diffusion directions and 3b values for each direction. Mean kurtosis (MK), mean diffusivity and fractional anisotropy (FA) of cortical and subcortical GM were measured using histogram analysis. Spearman rank correlations were used to characterize associations among imaging measures and clinical/neuropsychological scores. RESULTS: In cortical GM, a significant decrease of MK (0.68 vs. 0.73; p < 0.001) and increase of FA (0.16 vs. 0.13; p < 0.001) was found in patients compared to controls. Decreased cortical MK was correlated with poor performance on the Delis-Kaplan Executive Function System test (r = 0.66, p = 0.01). CONCLUSION: Mean kurtosis is sensitive to abnormality in GM of MS patients and can provide information that is complementary to that of conventional DTI-derived metrics. The association between MK and cognitive deficits suggests that DKI might serve as a clinically relevant biomarker for cortical injury.

Altered microstructure in temporal lobe epilepsy: a diffusional kurtosis imaging study.

BACKGROUND AND PURPOSE: Temporal lobe epilepsy is associated with regional abnormalities in tissue microstructure, as demonstrated by DTI. However, the full extent of these abnormalities has not yet been defined because DTI conveys only a fraction of the information potentially accessible with diffusion MR imaging. In this study, we assessed the added value of diffusional kurtosis imaging, an extension of DTI, to evaluate microstructural abnormalities in patients with temporal lobe epilepsy. MATERIALS AND METHODS: Thirty-two patients with left temporal lobe epilepsy and 36 matched healthy subjects underwent diffusion MR imaging. To evaluate abnormalities in patients, we performed voxelwise analyses, assessing DTI-derived mean diffusivity, fractional anisotropy, and diffusional kurtosis imaging-derived mean diffusional kurtosis, as well as diffusional kurtosis imaging and DTI-derived axial and radial components, comparing patients with controls. RESULTS: We replicated findings from previous studies demonstrating a reduction in fractional anisotropy and an increase in mean diffusivity preferentially affecting, but not restricted to, the temporal lobe ipsilateral to seizure onset. We also noted a pronounced pattern of diffusional kurtosis imaging abnormalities in gray and white matter tissues, often extending into regions that were not detected as abnormal by DTI measures. CONCLUSIONS: Diffusional kurtosis is a sensitive and complementary measure of microstructural compromise in patients with temporal lobe epilepsy. It provides additional information regarding the anatomic distribution and degree of damage in this condition. Diffusional kurtosis imaging may be used as a biomarker for disease severity, clinical phenotypes, and treatment monitoring in epilepsy.

Diffusional kurtosis imaging reveals a distinctive pattern of microstructural alternations in idiopathic generalized epilepsy.

OBJECTIVES: Idiopathic generalized epilepsy (IGE) arises from paroxysmal dysfunctions of the thalamo-cortical network. One of the hallmarks of IGE is the absence of visible abnormalities on routine magnetic resonance imaging (MRI). However, recent quantitative MRI studies showed cortical-subcortical structural abnormalities in IGE, but the extent of abnormalities has been inconsistent in the literature. The inconsistencies may be associated with complex microstructural abnormalities in IGE that are not completely detectable using conventional diffusion tensor imaging methods. The goal of this study was to investigate white-matter (WM) microstructural abnormalities in patients with IGE using diffusional kurtosis imaging (DKI). MATERIALS AND METHODS: We obtained DKI and volumetric T1-weighted images from 14 patients with IGE and 25 matched healthy controls. Using tract-based spatial statistics, we performed voxel-wise group comparisons in the parametric maps generated from DKI: mean diffusivity (MD), fractional anisotropy (FA), and mean kurtosis (MK), and in probabilistic maps of WM volume generated by voxel-based morphometry. RESULTS: We observed that conventional microstructural measures (MD and FA) revealed WM abnormalities in thalamo-cortical projections, whereas MK disclosed a broader pattern of WM abnormalities involving thalamo-cortical and cortical-cortical projections. CONCLUSIONS: Even though IGE is traditionally considered a 'non-lesional' form of epilepsy, our results demonstrated pervasive thalamo-cortical WM microstructural abnormalities. Particularly, WM abnormalities shown by MK further extended into cortical-cortical projections. This suggests that the extent of microstructural abnormalities in thalamo-cortical projections in IGE may be better assessed through the diffusion metrics provided by DKI.

Diffusional kurtosis imaging of the developing brain.

BACKGROUND AND PURPOSE: Diffusional kurtosis imaging is an extension of DTI but includes non-Gaussian diffusion effects, allowing more comprehensive characterization of microstructural changes during brain development. Our purpose was to use diffusional kurtosis imaging to measure age-related microstructural changes in both the WM and GM of the developing human brain. MATERIALS AND METHODS: Diffusional kurtosis imaging was performed in 59 subjects ranging from birth to 4 years 7 months of age. Diffusion metrics, fractional anisotropy, and mean kurtosis were collected from VOIs within multiple WM and GM structures and subsequently analyzed with respect to age. Diffusional kurtosis tractography images at various stages of development were also generated. RESULTS: Fractional anisotropy and mean kurtosis both showed age-related increases in all WM regions, reflecting progression of diffusional anisotropy throughout development, predominantly in the first 2 years of life (eg, 70% and 157% increase in fractional anisotropy and mean kurtosis, respectively, from birth to 2 years for the splenium). However, mean kurtosis detected continued microstructural changes in WM past the fractional anisotropy plateau, accounting for more delayed isotropic changes (eg, 90% of maximum fractional anisotropy was reached at 5 months, whereas 90% of maximum mean kurtosis occurred at 18 months for the external capsule). Mean kurtosis may also provide greater characterization of GM maturation (eg, the putamen showed no change in fractional anisotropy but an 81% change in mean kurtosis from birth to 4 years 7 months). CONCLUSIONS: Mean kurtosis detects significant microstructural changes consistent with known patterns of brain maturation. In comparison with fractional anisotropy, mean kurtosis may offer a more comprehensive evaluation of age-related microstructural changes in both WM and GM and is potentially a valuable technique for studying brain development.

Hot topics in functional neuroradiology.

Functional neuroradiology represents a relatively new and ever-growing subspecialty in the field of neuroradiology. Neuroradiology has evolved beyond anatomy and basic tissue signal characteristics and strives to understand the underlying physiologic processes of central nervous system disease. The American Society of Functional Neuroradiology sponsors a yearly educational and scientific meeting, and the educational committee was asked to suggest a few cutting-edge functional neuroradiology techniques (hot topics). The following is a review of several of these topics and includes "Diffusion Tensor Imaging of the Pediatric Spinal Cord"; "Diffusional Kurtosis Imaging"; "From Standardization to Quantification: Beyond Biomarkers toward Bioscales as Neuro MR Imaging Surrogates of Clinical End Points"; Resting-State Functional MR Imaging"; and "Current Use of Cerebrovascular Reserve Imaging."

Novel white matter tract integrity metrics sensitive to Alzheimer disease progression.

BACKGROUND AND PURPOSE: Along with cortical abnormalities, white matter microstructural changes such as axonal loss and myelin breakdown are implicated in the pathogenesis of Alzheimer disease. Recently, a white matter model was introduced that relates non-Gaussian diffusional kurtosis imaging metrics to characteristics of white matter tract integrity, including the axonal water fraction, the intra-axonal diffusivity, and the extra-axonal axial and radial diffusivities. MATERIALS AND METHODS: This study reports these white matter tract integrity metrics in subjects with amnestic mild cognitive impairment (n = 12), Alzheimer disease (n = 14), and age-matched healthy controls (n = 15) in an effort to investigate their sensitivity, diagnostic accuracy, and associations with white matter changes through the course of Alzheimer disease. RESULTS: With tract-based spatial statistics and region-of-interest analyses, increased diffusivity in the extra-axonal space (extra-axonal axial and radial diffusivities) in several white matter tracts sensitively and accurately discriminated healthy controls from those with amnestic mild cognitive impairment (area under the receiver operating characteristic curve = 0.82-0.95), while widespread decreased axonal water fraction discriminated amnestic mild cognitive impairment from Alzheimer disease (area under the receiver operating characteristic curve = 0.84). Additionally, these white matter tract integrity metrics in the body of the corpus callosum were strongly correlated with processing speed in amnestic mild cognitive impairment (r = |0.80-0.82|, P < .001). CONCLUSIONS: These findings have implications for the course and spatial progression of white matter degeneration in Alzheimer disease, suggest the mechanisms by which these changes occur, and demonstrate the viability of these white matter tract integrity metrics as potential neuroimaging biomarkers of the earliest stages of Alzheimer disease and disease progression.

Cognitive impairment in mild traumatic brain injury: a longitudinal diffusional kurtosis and perfusion imaging study.

BACKGROUND AND PURPOSE: Cognitive impairment is frequent among patients with mild traumatic brain injury despite the absence of detectable damage on conventional MR imaging. In this study, the quantitative MR imaging techniques DTI, DKI, and ASL were used to measure changes in the structure and function in the thalamus and WM of patients with MTBI during a short follow-up period, to determine whether these techniques can be used to investigate relationships with cognitive performance and to predict outcome. MATERIALS AND METHODS: Twenty patients with MTBI and 16 controls underwent MR imaging at 3T and a neuropsychological battery designed to yield measures for attention, concentration, executive functioning, memory, learning, and information processing. MK, FA, MD, and CBF were measured in the thalamus by using region-of-interest analysis and in WM by using tract-based spatial statistics. Analyses were performed comparing regional imaging measures of subject groups and the results of testing of their associations with neuropsychological performance. RESULTS: Patients with MTBI exhibited significant differences from controls for DTI, DKI, and ASL measures in the thalamus and various WM regions both within 1 month after injury and >9 months after injury. At baseline, DTI and DKI measures in the thalamus and various WM regions were significantly associated with performance in different neuropsychological domains, and cognitive impairment was significantly associated with MK in the thalamus and FA in optic radiations. CONCLUSIONS: Combined application of DTI, DKI, and ASL to study MTBI might be useful for investigating dynamic changes in the thalamus and WM as well as cognitive impairment during a short follow-up period, though the small number of patients examined did not predict outcome.

Brain iron quantification in mild traumatic brain injury: a magnetic field correlation study.

BACKGROUND AND PURPOSE: Experimental studies have suggested a role for iron accumulation in the pathology of TBI. Magnetic field correlation MR imaging is sensitive to the presence of non-heme iron. The aims of this study are to 1) assess the presence, if any, and the extent of iron deposition in the deep gray matter and regional white matter of patients with mTBI by using MFC MR imaging; and 2) investigate the association of regional brain iron deposition with cognitive and behavioral performance of patients with mTBI. MATERIALS AND METHODS: We prospectively enrolled 28 patients with mTBI. Eighteen healthy subjects served as controls. The subjects were administered the Stroop color word test, the Verbal Fluency Task, and the Post-Concussion Symptoms Scale. The MR imaging protocol (on a 3T imager) consisted of conventional brain imaging and MFC sequences. After the calculation of parametric maps, MFC was measured by using a region of interest approach. MFC values across groups were compared by using analysis of covariance, and the relationship of MFC values and neuropsychological tests were evaluated by using Spearman correlations. RESULTS: Compared with controls, patients with mTBI demonstrated significant higher MFC values in the globus pallidus (P = .002) and in the thalamus (P = .036). In patients with mTBI, Stroop test scores were associated with the MFC value in frontal white matter (r = -0.38, P = .043). CONCLUSIONS: MFC values were significantly elevated in the thalamus and globus pallidus of patients with mTBI, suggesting increased accumulation of iron. This supports the hypothesis that deep gray matter is a site of injury in mTBI and suggests a possible role for iron accumulation in the pathophysiological events after mTBI.

Intravoxel incoherent motion imaging of tumor microenvironment in locally advanced breast cancer.

Diffusion-weighted imaging plays important roles in cancer diagnosis, monitoring, and treatment. Although most applications measure restricted diffusion by tumor cellularity, diffusion-weighted imaging is also sensitive to vascularity through the intravoxel incoherent motion effect. Hypervascularity can confound apparent diffusion coefficient measurements in breast cancer. We acquired multiple b-value diffusion-weighted imaging at 3 T in a cohort of breast cancer patients and performed biexponential intravoxel incoherent motion analysis to extract tissue diffusivity (D(t)), perfusion fraction (f(p)), and pseudodiffusivity (D(p)). Results indicated significant differences between normal fibroglandular tissue and malignant lesions in apparent diffusion coefficient mean (±standard deviation) values (2.44 ± 0.30 vs. 1.34 ± 0.39 µm(2)/msec, P < 0.01) and D(t) (2.36 ± 0.38 vs. 1.15 ± 0.35 µm(2)/msec, P < 0.01). Lesion diffusion-weighted imaging signals demonstrated biexponential character in comparison to monoexponential normal tissue. There is some differentiation of lesion subtypes (invasive ductal carcinoma vs. other malignant lesions) with f(p) (10.5 ± 5.0% vs. 6.9 ± 2.9%, P = 0.06), but less so with D(t) (1.14 ± 0.32 µm(2)/msec vs. 1.18 ± 0.52 µm(2)/msec, P = 0.88) and D(p) (14.9 ± 11.4 µm(2)/msec vs. 16.1 ± 5.7 µm(2)/msec, P = 0.75). Comparison of intravoxel incoherent motion biomarkers with contrast enhancement suggests moderate correlations. These results suggest the potential of intravoxel incoherent motion vascular and cellular biomarkers for initial grading, progression monitoring, or treatment assessment of breast tumors.

Predicting grade of cerebral glioma using vascular-space occupancy MR imaging.

BACKGROUND AND PURPOSE: MR imaging can measure tissue perfusion and the integrity of the blood-brain barrier. We hypothesize that a combined measure of cerebral blood volume and vascular permeability using vascular-space occupancy (VASO) MR imaging, a recently developed imaging technique, is of diagnostic value for predicting tumor grade. MATERIALS AND METHODS: Thirty-nine patients (9 World Health Organization [WHO] grade II, 20 grade III, and 10 grade IV as determined by histopathologic assessment) were examined using VASO MR imaging, and regions-of-interest analysis was performed in tumoral regions, as well as in regions contralateral to the tumor. A Mann-Whitney test was conducted on the resulting VASO indices for a pairwise comparison across tumor grades. Nominal logistic regression was used to evaluate the use of VASO parameters for predicting group membership (by the percentage of correct classifications). RESULTS: The ratio between tumor side and contralateral side, VASO(Ratio), showed significant differences in all 3 of the pairwise comparisons (P < .01). VASO values in the tumoral regions, VASO(Tumor), showed significant difference between grade II and III and between II and IV but not between III and IV. Both VASO(Tumor) and VASO(Ratio) were found to be significant predictors of tumor grade, giving diagnostic accuracies of 66.7% and 71.8%, respectively. When testing to discriminate grade II tumors from higher grade tumors, the areas under the receiver operating characteristic curve were found to be 0.974 and 0.985 for VASO(Tumor) and VASO(Ratio), respectively. CONCLUSION: VASO MR imaging can be used for noninvasive tumor grade prediction based on cerebral blood volume and vascular permeability. VASO is more effective in separating WHO grade II from higher grades than in separating grade III from grade IV.