Relationships of Cognitive Measures with Cerebrospinal Fluid but Not Imaging Biomarkers of Alzheimer Disease Vary between Black and White Individuals.

OBJECTIVE: Biomarkers of Alzheimer disease vary between groups of self-identified Black and White individuals in some studies. This study examined whether the relationships between biomarkers or between biomarkers and cognitive measures varied by racialized groups. METHODS: Cerebrospinal fluid (CSF), amyloid positron emission tomography (PET), and magnetic resonance imaging measures were harmonized across four studies of memory and aging. Spearman correlations between biomarkers and between biomarkers and cognitive measures were calculated within each racialized group, then compared between groups by standard normal tests after Fisher's Z-transformations. RESULTS: The harmonized dataset included at least one biomarker measurement from 495 Black and 2,600 White participants. The mean age was similar between racialized groups. However, Black participants were less likely to have cognitive impairment (28% vs 36%) and had less abnormality of some CSF biomarkers including CSF Aß42/40, total tau, p-tau181, and neurofilament light. CSF Aß42/40 was negatively correlated with total tau and p-tau181 in both groups, but at a smaller magnitude in Black individuals. CSF Aß42/40, total tau, and p-tau181 had weaker correlations with cognitive measures, especially episodic memory, in Black than White participants. Correlations of amyloid measures between CSF (Aß42/40, Aß42) and PET imaging were also weaker in Black than White participants. Importantly, no differences based on race were found in correlations between different imaging biomarkers, or in correlations between imaging biomarkers and cognitive measures. INTERPRETATION: Relationships between CSF biomarkers but not imaging biomarkers varied by racialized groups. Imaging biomarkers performed more consistently across racialized groups in associations with cognitive measures. ANN NEUROL 2024;95:495-506.

Impact of white matter networks on risk for memory decline following resection versus ablation in temporal lobe epilepsy.

BACKGROUND: With expanding neurosurgical options in epilepsy, it is important to characterise each options' risk for postoperative cognitive decline. Here, we characterise how patients' preoperative white matter (WM) networks relates to postoperative memory changes following different epilepsy surgeries. METHODS: Eighty-nine patients with temporal lobe epilepsy with T1-weighted and diffusion-weighted imaging as well as preoperative and postoperative verbal memory scores (prose recall) underwent either anterior temporal lobectomy (ATL: n=38) or stereotactic laser amygdalohippocampotomy (SLAH; n=51). We computed laterality indices (ie, asymmetry) for volume of the hippocampus and fractional anisotropy (FA) of two deep WM tracts (uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF)). RESULTS: Preoperatively, left-lateralised FA of the ILF was associated with higher prose recall (p<0.01). This pattern was not observed for the UF or hippocampus (ps>0.05). Postoperatively, right-lateralised FA of the UF was associated with less decline following left ATL (p<0.05) but not left SLAH (p>0.05), while right-lateralised hippocampal asymmetry was associated with less decline following both left ATL and SLAH (ps<0.05). After accounting for preoperative memory score, age of onset and hippocampal asymmetry, the association between UF and memory decline in left ATL remained significant (p<0.01). CONCLUSIONS: Asymmetry of the hippocampus is an important predictor of risk for memory decline following both surgeries. However, asymmetry of UF integrity, which is only severed during ATL, is an important predictor of memory decline after ATL only. As surgical procedures and pre-surgical mapping evolve, understanding the role of frontal-temporal WM in memory networks could help to guide more targeted surgical approaches to mitigate cognitive decline.

Magnetic resonance evidence of increased iron content in subcortical brain regions in asymptomatic Alzheimer's disease.

While iron over-accumulation has been reported in late stage Alzheimer's disease (AD), whether this occurs early in the asymptomatic stage of AD remains unknown. We aimed to assess brain iron levels in asymptomatic AD using quantitative MR relaxometry of effective transverse relaxation rate (R2*) and longitudinal relaxation rate (R1), and recruited 118 participants comprised of three groups including healthy young participants, and cognitively normal older individuals without or with positive AD biomarkers based on cerebrospinal fluid (CSF) proteomics analysis. Compared with the healthy young group, increased R2* was found in widespread cortical and subcortical regions in the older groups. Further, significantly higher levels of R2* were found in the cognitively normal older subjects with positive CSF AD biomarker (i.e., asymptomatic AD) compared with those with negative AD biomarker in subcortical regions including the left and right caudate, left and right putamen, and left and right globus pallidus (p < .05 for all regions), suggesting increased iron content in these regions. Subcortical R2* of some regions was found to significantly correlate with CSF AD biomarkers and neuropsychological assessments of visuospatial functions. In conclusion, R2* could be a valuable biomarker for studying early pathophysiological changes in AD.

Acetazolamide-augmented BOLD MRI to Assess Whole-Brain Cerebrovascular Reactivity in Chronic Steno-occlusive Disease Using Principal Component Analysis.

Background Exhaustion of cerebrovascular reactivity (CVR) portends increased stroke risk. Acetazolamide-augmented blood oxygenation level-dependent (BOLD) MRI has been used to estimate CVR, but low signal-to-noise conditions relegate its use to terminal CVR (CVRend) measurements that neglect dynamic features of CVR. Purpose To demonstrate comprehensive characterization of acetazolamide-augmented BOLD MRI response in chronic steno-occlusive disease using a computational framework to precondition signal time courses for dynamic whole-brain CVR analysis. Materials and Methods This study focused on retrospective analysis of consecutive patients with unilateral chronic steno-occlusive disease who underwent acetazolamide-augmented BOLD imaging for recurrent minor stroke or transient ischemic attack at an academic medical center between May 2017 and October 2020. A custom principal component analysis-based denoising pipeline was used to correct spatially varying non-signal-bearing contributions obtained by a local principal component analysis of the MRI time series. Standard voxelwise CVRend maps representing terminal responses were produced and compared with maximal CVR (CVRmax) as isolated from binned (per-repetition time) denoised BOLD time course. A linear mixed-effects model was used to compare CVRmax and CVRend in healthy and diseased hemispheres. Results A total of 23 patients (median age, 51 years; IQR, 42-61, 13 men) who underwent 32 BOLD examinations were included. Processed MRI data showed twofold improvement in signal-to-noise ratio, allowing improved isolation of dynamic characteristics in signal time course for sliding window CVRmax analysis to the level of each BOLD repetition time (approximately 2 seconds). Mean CVRmax was significantly higher than mean CVRend in diseased (5.2% vs 3.8%, P < .01) and healthy (5.5% vs 4.0%, P < .01) hemispheres. Several distinct time-signal signatures were observed, including nonresponsive; delayed/blunted; brisk; and occasionally nonmonotonic time courses with paradoxical features in normal and abnormal tissues (ie, steal and reverse-steal patterns). Conclusion A principal component analysis-based computational framework for analysis of acetazolamide-augmented BOLD imaging can be used to measure unsustained CVRmax through twofold improvements in signal-to-noise ratio. © RSNA, 2023 Supplemental material is available for this article.

Robust quantitative susceptibility mapping via approximate message passing with parameter estimation.

PURPOSE: For quantitative susceptibility mapping (QSM), the lack of ground-truth in clinical settings makes it challenging to determine suitable parameters for the dipole inversion. We propose a probabilistic Bayesian approach for QSM with built-in parameter estimation, and incorporate the nonlinear formulation of the dipole inversion to achieve a robust recovery of the susceptibility maps. THEORY: From a Bayesian perspective, the image wavelet coefficients are approximately sparse and modeled by the Laplace distribution. The measurement noise is modeled by a Gaussian-mixture distribution with two components, where the second component is used to model the noise outliers. Through probabilistic inference, the susceptibility map and distribution parameters can be jointly recovered using approximate message passing (AMP). METHODS: We compare our proposed AMP with built-in parameter estimation (AMP-PE) to the state-of-the-art L1-QSM, FANSI, and MEDI approaches on the simulated and in vivo datasets, and perform experiments to explore the optimal settings of AMP-PE. Reproducible code is available at: https://github.com/EmoryCN2L/QSM_AMP_PE. RESULTS: On the simulated Sim2Snr1 dataset, AMP-PE achieved the lowest NRMSE, deviation from calcification moment and the highest SSIM, while MEDI achieved the lowest high-frequency error norm. On the in vivo datasets, AMP-PE is robust and successfully recovers the susceptibility maps using the estimated parameters, whereas L1-QSM, FANSI and MEDI typically require additional visual fine-tuning to select or double-check working parameters. CONCLUSION: AMP-PE provides automatic and adaptive parameter estimation for QSM and avoids the subjectivity from the visual fine-tuning step, making it an excellent choice for the clinical setting.

Diaschisis Profiles in the Cerebellar Response to Hemodynamic Stimuli: Insights From Dynamic Measurement of Cerebrovascular Reactivity to Identify Occult and Transient Maxima.

BACKGROUND: Crossed cerebellar diaschisis (CCD) refers to depressions in perfusion and metabolism within the cerebellar hemisphere contralateral to supratentorial disease. Prior investigation into CCD in cerebrovascular reactivity (CVR) has been limited to terminal CVR estimations (CVRend ). We recently have demonstrated the presence of unsustained CVR maxima (CVRmax ) using dynamic CVR analysis, offering a fully dynamic characterization of CVR to hemodynamic stimuli. PURPOSE: To investigate CCD in CVRmax from dynamic blood oxygen level-dependent (BOLD) MRI, by comparison with conventional CVRend estimation. STUDY TYPE: Retrospective. POPULATION: A total of 23 patients (median age: 51 years, 10 females) with unilateral chronic steno-occlusive cerebrovascular disease, without prior knowledge of CCD status. FIELD STRENGTH/SEQUENCE: A 3-T, T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) and acetazolamide-augmented BOLD imaging performed with a gradient-echo echo-planar imaging (EPI) sequence. ASSESSMENT: A custom denoising pipeline was used to generate BOLD-CVR time signals. CVRend was established using the last minute of the BOLD response relative to the first-minute baseline. Following classification of healthy versus diseased cerebral hemispheres, CVRmax and CVRend were calculated for bilateral cerebral and cerebellar hemispheres. Three independent observers evaluated all data for the presence of CCD. STATISTICAL TESTS: Pearson correlations for comparing CVR across hemispheres, two-proportion Z-tests for comparing CCD prevalence, and Wilcoxon signed-rank tests for comparing median CVR. The level of statistical significance was set at P ≤ 0.05. RESULTS: CCD-related changes were observed on both CVRend and CVRmax maps, with all CCD+ cases identifiable by inspection of either map. Diseased cerebral and contralateral cerebellar hemispheric CVR correlations in CCD+ patients were stronger when using CVRend (r = 0.728) as compared to CVRmax (r = 0.676). CVR correlations between healthy cerebral hemispheres and contralateral cerebellar hemispheres were stronger for CVRmax (r = 0.739) than for CVRend (r = 0.705). DATA CONCLUSION: CCD-related alterations could be observed in CVR examinations. Conventional CVRend may underestimate CVR and could exaggerate CCD. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 3.

A phase II study repurposing atomoxetine for neuroprotection in mild cognitive impairment.

The locus coeruleus is the initial site of Alzheimer's disease neuropathology, with hyperphosphorylated Tau appearing in early adulthood followed by neurodegeneration in dementia. Locus coeruleus dysfunction contributes to Alzheimer's pathobiology in experimental models, which can be rescued by increasing norepinephrine transmission. To test norepinephrine augmentation as a potential disease-modifying therapy, we performed a biomarker-driven phase II trial of atomoxetine, a clinically-approved norepinephrine transporter inhibitor, in subjects with mild cognitive impairment due to Alzheimer's disease. The design was a single-centre, 12-month double-blind crossover trial. Thirty-nine participants with mild cognitive impairment and biomarker evidence of Alzheimer's disease were randomized to atomoxetine or placebo treatment. Assessments were collected at baseline, 6- (crossover) and 12-months (completer). Target engagement was assessed by CSF and plasma measures of norepinephrine and metabolites. Prespecified primary outcomes were CSF levels of IL1α and TECK. Secondary/exploratory outcomes included clinical measures, CSF analyses of amyloid-ß42, Tau, and pTau181, mass spectrometry proteomics and immune-based targeted inflammation-related cytokines, as well as brain imaging with MRI and fluorodeoxyglucose-PET. Baseline demographic and clinical measures were similar across trial arms. Dropout rates were 5.1% for atomoxetine and 2.7% for placebo, with no significant differences in adverse events. Atomoxetine robustly increased plasma and CSF norepinephrine levels. IL-1α and TECK were not measurable in most samples. There were no significant treatment effects on cognition and clinical outcomes, as expected given the short trial duration. Atomoxetine was associated with a significant reduction in CSF Tau and pTau181 compared to placebo, but not associated with change in amyloid-ß42. Atomoxetine treatment also significantly altered CSF abundances of protein panels linked to brain pathophysiologies, including synaptic, metabolism and glial immunity, as well as inflammation-related CDCP1, CD244, TWEAK and osteoprotegerin proteins. Treatment was also associated with significantly increased brain-derived neurotrophic factor and reduced triglycerides in plasma. Resting state functional MRI showed significantly increased inter-network connectivity due to atomoxetine between the insula and the hippocampus. Fluorodeoxyglucose-PET showed atomoxetine-associated increased uptake in hippocampus, parahippocampal gyrus, middle temporal pole, inferior temporal gyrus and fusiform gyrus, with carry-over effects 6 months after treatment. In summary, atomoxetine treatment was safe, well tolerated and achieved target engagement in prodromal Alzheimer's disease. Atomoxetine significantly reduced CSF Tau and pTau, normalized CSF protein biomarker panels linked to synaptic function, brain metabolism and glial immunity, and increased brain activity and metabolism in key temporal lobe circuits. Further study of atomoxetine is warranted for repurposing the drug to slow Alzheimer's disease progression.

A probabilistic Bayesian approach to recover R2*$$ {R}_{2\ast } $$ map and phase images for quantitative susceptibility mapping.

PURPOSE: Undersampling is used to reduce the scan time for high-resolution three-dimensional magnetic resonance imaging. In order to achieve better image quality and avoid manual parameter tuning, we propose a probabilistic Bayesian approach to recover R2∗$$ {R}_2^{\ast } $$ map and phase images for quantitative susceptibility mapping (QSM), while allowing automatic parameter estimation from undersampled data. THEORY: Sparse prior on the wavelet coefficients of images is interpreted from a Bayesian perspective as sparsity-promoting distribution. A novel nonlinear approximate message passing (AMP) framework that incorporates a mono-exponential decay model is proposed. The parameters are treated as unknown variables and jointly estimated with image wavelet coefficients. METHODS: Undersampling takes place in the y-z plane of k-space according to the Poisson-disk pattern. Retrospective undersampling is performed to evaluate the performances of different reconstruction approaches, prospective undersampling is performed to demonstrate the feasibility of undersampling in practice. RESULTS: The proposed AMP with parameter estimation (AMP-PE) approach successfully recovers R2∗$$ {R}_2^{\ast } $$ maps and phase images for QSM across various undersampling rates. It is more computationally efficient, and performs better than the state-of-the-art l1$$ {l}_1 $$ -norm regularization (L1) approach in general, except a few cases where the L1 approach performs as well as AMP-PE. CONCLUSION: AMP-PE achieves better performance by drawing information from both the sparse prior and the mono-exponential decay model. It does not require parameter tuning, and works with a clinical, prospective undersampling scheme where parameter tuning is often impossible or difficult due to the lack of ground-truth image.

Atrophy and cognitive profiles in older adults with temporal lobe epilepsy are similar to mild cognitive impairment.

Epilepsy incidence and prevalence peaks in older adults yet systematic studies of brain ageing and cognition in older adults with epilepsy remain limited. Here, we characterize patterns of cortical atrophy and cognitive impairment in 73 older adults with temporal lobe epilepsy (>55 years) and compare these patterns to those observed in 70 healthy controls and 79 patients with amnestic mild cognitive impairment, the prodromal stage of Alzheimer's disease. Patients with temporal lobe epilepsy were recruited from four tertiary epilepsy surgical centres; amnestic mild cognitive impairment and control subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Whole brain and region of interest analyses were conducted between patient groups and controls, as well as between temporal lobe epilepsy patients with early-onset (age of onset <50 years) and late-onset (>50 years) seizures. Older adults with temporal lobe epilepsy demonstrated a similar pattern and magnitude of medial temporal lobe atrophy to amnestic mild cognitive impairment. Region of interest analyses revealed pronounced medial temporal lobe thinning in both patient groups in bilateral entorhinal, temporal pole, and fusiform regions (all P < 0.05). Patients with temporal lobe epilepsy demonstrated thinner left entorhinal cortex compared to amnestic mild cognitive impairment (P = 0.02). Patients with late-onset temporal lobe epilepsy had a more consistent pattern of cortical thinning than patients with early-onset epilepsy, demonstrating decreased cortical thickness extending into the bilateral fusiform (both P < 0.01). Both temporal lobe epilepsy and amnestic mild cognitive impairment groups showed significant memory and language impairment relative to healthy control subjects. However, despite similar performances in language and memory encoding, patients with amnestic mild cognitive impairment demonstrated poorer delayed memory performances relative to both early and late-onset temporal lobe epilepsy. Medial temporal lobe atrophy and cognitive impairment overlap between older adults with temporal lobe epilepsy and amnestic mild cognitive impairment highlights the risks of growing old with epilepsy. Concerns regarding accelerated ageing and Alzheimer's disease co-morbidity in older adults with temporal lobe epilepsy suggests an urgent need for translational research aimed at identifying common mechanisms and/or targeting symptoms shared across a broad neurological disease spectrum.

Which multiband factor should you choose for your resting-state fMRI study?

Multiband acquisition, also called simultaneous multislice, has become a popular technique in resting-state functional connectivity studies. Multiband (MB) acceleration leads to a higher temporal resolution but also leads to spatially heterogeneous noise amplification, suggesting the costs may be greater in areas such as the subcortex. We evaluate MB factors of 2, 3, 4, 6, 8, 9, and 12 with 2 mm isotropic voxels, and additionally 2 mm and 3.3 mm single-band acquisitions, on a 32-channel head coil. Noise amplification was greater in deeper brain regions, including subcortical regions. Correlations were attenuated by noise amplification, which resulted in spatially varying biases that were more severe at higher MB factors. Temporal filtering decreased spatial biases in correlations due to noise amplification, but also tended to decrease effect sizes. In seed-based correlation maps, left-right putamen connectivity and thalamo-motor connectivity were highest in the single-band 3.3 mm protocol. In correlation matrices, MB 4, 6, and 8 had a greater number of significant correlations than the other acquisitions (both with and without temporal filtering). We recommend single-band 3.3 mm for seed-based subcortical analyses, and MB 4 provides a reasonable balance for studies analyzing both seed-based correlation maps and connectivity matrices. In multiband studies including secondary analyses of large-scale datasets, we recommend reporting effect sizes or test statistics instead of correlations. If correlations are reported, temporal filtering (or another method for thermal noise removal) should be used. The Emory Multiband Dataset is available on OpenNeuro.

Simultaneous perfusion and permeability assessments using multiband multi-echo EPI (M2-EPI) in brain tumors.

PURPOSE: To study a multiband multi-echo EPI (M2-EPI) sequence for dynamic susceptibility contrast (DSC) perfusion imaging with leakage correction and vascular permeability measurements, and to evaluate the benefits of increased temporal resolution provided by this acquisition strategy on the accuracy of perfusion and permeability estimations. METHODS: A novel M2-EPI sequence was developed, and a pharmacokinetic model accounting for contrast agent extravasation was used to produce perfusion maps and additional vascular permeability maps. The advantage of M2-EPI for DSC perfusion imaging was demonstrated in vivo in 5 patients with brain tumors, and numerical simulations were performed to evaluate the advantage of improved temporal resolution afforded by the technique. RESULTS: In contrast to underestimations of cerebral blood volume (CBV) in tumors using the single-echo acquisition strategy, M2-EPI provided more plausible estimates of CBV. A quantitative evaluation showed higher estimated values of CBV and mean transit time in tumor tissues using M2-EPI (CBV: 3.08 ± 0.78 mL/100 g versus 1.56 ± 1.38 mL/100 g [P = .006]; mean transit time: 4.94 ± 1.17 seconds versus 1.83 ± 2.06 seconds [P = 0.033]). Numerical simulations showed that higher temporal resolution provided by M2-EPI was associated with more accurate estimates of cerebral blood flow, CBV, and permeability parameters. CONCLUSION: The novel M2-EPI acquisition strategy for DSC imaging facilitates leakage-corrected perfusion measurements with additional permeability assessments and more accurate estimates of perfusion/permeability parameters, and may be used as a quantitative tool for the diagnosis, prognosis, and treatment monitoring of brain tumors.

Cerebral MR oximetry during acetazolamide augmentation: Beyond cerebrovascular reactivity in hemodynamic failure.

BACKGROUND: Oxygen extraction fraction (OEF) elevation predicts increased ischemic stroke incidence among patients with carotid steno-occlusive disease, and can be estimated from quantitative susceptibility mapping (QSM) MRI. PURPOSE: To explore QSM oximetry during acetazolamide (ACZ) challenge, hypothesizing that detectable OEF alterations will reflect hemodynamic compromise in unilateral cerebrovascular disease (CVD) patients. STUDY TYPE: Retrospective. SUBJECTS: Fourteen unilateral CVD patients, and 24 healthy controls (HC). FIELD STRENGTH/SEQUENCE: Multiecho gradient echo (GRE) and T1 -weighted images at 3T. ASSESSMENT: We constructed QSM images and R2* maps from multiecho GRE images. QSM-OEF maps were generated from the susceptibility difference between venous blood and background brain tissue. Intrasubject diseased/contralateral hemisphere OEF ratios in the middle cerebral artery (MCA) territories were calculated. Intravascular susceptibility in the straight sinus (SS) and MCA was also measured. STATISTICAL TESTS: The result significance was determined using t-tests and Pearson's correlation. RESULTS: Mean and standard deviation for the patient diseased/contralateral OEF ratios were 1.15 ± 0.14 at baseline and 1.23 ± 0.17 post-ACZ. Disease group R2* ratios were 0.95 ± 0.05 at baseline and 1.03 ± 0.08 post-ACZ. Left/right OEF and R2* ratios for the HC group were 0.98 ± 0.06 and 0.99 ± 0.038, respectively. Susceptibility (ppb) in the SS and MCA in patients was 162.63 ± 35.4 and -22.33 ± 13.70, respectively, at baseline, 124.56 ± 37.43 and -19.27 ± 23.14 post-ACZ. The HC group SS and MCA susceptibility was 146.10 ± 24.79 and -19.59 ± 12.37, respectively. Patient group OEF ratios were greater than 1.0 before and after ACZ challenge (P < 0.01 and < 0.001, respectively, one-sample t-test), and were greater than HC ratios (P < 0.001 unpaired t-test). OEF and R2* ratios increased from baseline to post-ACZ (P = 0.024, 0.004, respectively, paired t-test). Detectable blood oxygenation change was confirmed by finding SS susceptibility decreased from baseline to post-ACZ (P < 0.001, paired t-test), while MCA susceptibility did not change significantly (P = 0.67, paired t-test). DATA CONCLUSION: These results suggest QSM is sensitive to dynamic OEF modulation during hemodynamic augmentation. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:175-182.

Proper timing for the evaluation of neonatal brain white matter development: a diffusion tensor imaging study.

OBJECTIVE: We aimed to determine the timing for assessing birth status of the developing brain (i.e. brain maturity at birth) by exploring the postnatal age-related changes in neonatal brain white matter (WM). METHODS: The institutional review board approved this study and all informed parental consents were obtained. 133 neonates (gestational age, 30-42 weeks) without abnormalities on MRI were studied with regard to WM development by diffusion tensor imaging-derived fractional anisotropy (FA). Tract-based spatial statistics (TBSS), locally-weighted scatterplot smoothing (LOESS) and piecewise linear-fitting were used to investigate the relationship between FA and postnatal age. FA along corticospinal tract (CST), optic radiation (OR), auditory radiation (AR) and thalamus-primary somatosensory cortex (thal-PSC) were extracted by automated fibre-tract quantification; their differences and associations with neonatal neurobehavioural scores at various postnatal age ranges were analysed by Wilcoxon's rank-sum test and Pearson's correlation. RESULTS: Using TBSS, postnatal age (days 1-28) positively correlated with FA in multiple WMs, including CST, OR, AR and thal-PSC (p<0.05). On the other hand, when narrowing the postnatal age window to days 1-14, no significant correlation was found, suggesting a biphasic WM development. LOESS and piecewise linear-fitting indicated that FA increased mildly before day 14 and its growth accelerated thereafter. Both FA and correlations with neurobehavioural scores in postnatal age range 2 (days 15-28) were significantly higher than in range 1 (days 1-14) (FA comparison: p<0.05; maximal correlation-coefficient: 0.693 vs. 0.169). CONCLUSION: Brain WM development during the neonatal stage includes two phases, i.e. a close-to-birth period within the first 14 days and a following accelerated maturation period. Therefore, evaluations of birth status should preferably be performed during the first period. KEY POINTS: • Brain white matter development within the first two postnatal weeks resembles a close-to-birth maturation. • Brain white matter development in the audio-visual, sensorimotor regions accelerates after two postnatal weeks. • Postnatal age-related effects should be considered in comparing preterm and term neonates.

Mechanisms and Risk Factors Contributing to Visual Field Deficits following Stereotactic Laser Amygdalohippocampotomy.

Selective laser amygdalohippocampotomy (SLAH) is a minimally invasive surgical treatment for medial temporal lobe epilepsy. Visual field deficits (VFDs) are a significant potential complication. The objective of this study was to determine the relationship between VFDs and potential mechanisms of injury to the optic radiations and lateral geniculate nucleus. We performed a retrospective cross-sectional analysis of 3 patients (5.2%) who developed persistent VFDs after SLAH within our larger series (n = 58), 15 healthy individuals and 10 SLAH patients without visual complications. Diffusion tractography was used to evaluate laser catheter penetration of the optic radiations. Using a complementary approach, we evaluated evidence for focal microstructural tissue damage within the optic radiations and lateral geniculate nucleus. Overablation and potential heat radiation were assessed by quantifying ablation and choroidal fissure CSF volumes as well as energy deposited during SLAH.SLAH treatment parameters did not distinguish VFD patients. Atypically high overlap between the laser catheter and optic radiations was found in 1/3 VFD patients and was accompanied by focal reductions in fractional anisotropy where the catheter entered the lateral occipital white matter. Surprisingly, lateral geniculate tissue diffusivity was abnormal following, but also preceding, SLAH in patients who subsequently developed a VFD (all p = 0.005).In our series, vision-related complications following SLAH, which appear to occur less frequently than following open temporal lobe -surgery, were not directly explained by SLAH treatment parameters. Instead, our data suggest that variations in lateral geniculate structure may influence susceptibility to indirect heat injury from transoccipital SLAH.

Cerebrospinal Fluid Pressure Reduction Results in Dynamic Changes in Optic Nerve Angle on Magnetic Resonance Imaging.

BACKGROUND: Optic nerve sheath tortuosity is a previously reported, but incompletely characterized, finding in idiopathic intracranial hypertension (IIH). We hypothesized that optic nerve angle (ONA), as a quantitative measure of tortuosity, would change dynamically with cerebrospinal fluid (CSF) pressure status of patients with IIH immediately before and after lumbar puncture (LP). METHODS: Consecutive patients with suspected IIH referred for MRI and diagnostic LP were prospectively enrolled in this single institution, institutional review board-approved study. Each patient underwent a pre-LP MRI, diagnostic LP with opening pressure (OP) and closing pressure (CP), and then post-LP MRI all within 1 session. Sagittal and axial ONAs were measured on multiplanar T2 SPACE images by 2 neuroradiologists on pre- and post-LP MRI. Effects of measured pressure and CSF volume removal on changes in ONA were analyzed as was interrater reliability for ONA measurement. RESULTS: Ten patients with IIH were included {all female, median age 29 (interquartile range [IQR] 25-32)}. All patients had elevated OP (median 37, IQR 34-41 cm H2O), and significantly reduced CP (median 18, IQR 16-19 cm H2O, P < 0.001) after CSF removal (IQR 13-16 mL). Within patients, mean ONAs (sagittal and axial) were significantly lower before (162 ± 9°, 163 ± 10°) than after (168 ± 7°, 169 ± 5°) LP (P = 0.001, 0.008, respectively). Interrater reliability was higher with sagittal ONA measurements (0.89) than axial (0.72). CONCLUSIONS: ONA changes with short-term CSF pressure reduction in patients with IIH, establishing optic nerve tortuosity as a dynamic process related to CSF status.

Disrupted interactions among the hippocampal, dorsal attention, and central-executive networks in amnestic mild cognitive impairment.

Neuroimaging investigations consistently demonstrate that the neural processes involve complex interactions between the large-scale networks. Among those networks, the dorsal attention network (DAN) and the central-executive network (CEN) have been previously shown to exhibit anti-correlated activity with the default-mode network (DMN) in cognitively normal people. In amnestic mild cognitive impairment (MCI) and Alzheimer's disease, the hippocampal network (HCN)-a key memory processing system-and its interactions with other networks have gathered central interest. The current study aims to evaluate the patterns of functional architectures of the HCN with the three networks-DAN, CEN, and DMN-in amnestic MCI and normal controls (NC) to test the hypothesis that the interactions of HCN with other networks alter in MCI. We recorded the resting state functional MRI, assessed patterns of functional architectures between the four networks using dynamical causal modeling, and compared between NC and MCI. Our analysis showed that the DAN modulates the activity between the HCN and the DMN in both MCI and NC. We further uncovered that the DAN modulates the activity between the HCN and the CEN in NC, but such modulation is impaired in MCI. We found an association between impaired modulation and Montreal cognitive assessment (R = 0.349). Overall, our findings provide important insight in understanding the neuroimaging signature of amnestic MCI and/or Alzheimer's disease.

Effects of Height and Blood Volume on Venous Enhancement After Gadolinium-Based Contrast Administration in MR Venography: A Paradigm Challenge and Implications for Clinical Imaging.

OBJECTIVE: The purpose of this study was to analyze quantitative and qualitative effects of estimated blood volume on venous enhancement in patients undergoing cerebral MR venography (MRV) with standard weight-based dosing of a gadolinium-based contrast agent. MATERIALS AND METHODS: Fifty-two patients with normal 1.5-T cerebral MRV findings and contemporaneous height and weight measurements were included. Estimated blood volume was calculated with the Nadler formula for blood volume. Standard weight-based cerebral MRV was performed after administration of gadobenate dimeglumine (0.1 mmol/kg up to 20 mL). Venous enhancement within the superior sagittal sinus, right jugular bulb, and left jugular bulb was measured. Patients were dichotomized on the basis of administration of less than versus a maximum weight-based gadolinium-based contrast dose of 20 mL. Venographic quality was assigned by two neuroradiologists. Correlational and multiple linear regression analyses were performed. RESULTS: Among patients receiving less than the maximum 20 mL of gadolinium, no significant correlations were observed between weight and vascular enhancement (p > 0.05). Significant correlations between height and enhancement were observed in the superior sagittal sinus and left jugular bulb. This finding suggests that differences in estimated blood volume driven by height remain unaccounted for (p < 0.05). With the 20-mL maximal dose, a significant inverse relation was noted between estimated blood volume and contrast enhancement of all vascular segments (p < 0.05). Within all vascular segments, significant correlations were observed between enhancement and user-defined quality scores (p < 0.05). This finding suggests that optimized dosing may affect reader confidence. CONCLUSION: Standard weight-based dosing for cerebral MRV insufficiently accounts for differences in circulating blood volume. An expanded biometric dosing paradigm leveraging readily attainable subject data may mitigate unintended variations in enhancement affecting venography and other clinical imaging modalities.

Noncontrast mapping of arterial delay and functional connectivity using resting-state functional MRI: a study in Moyamoya patients.

PURPOSE: To investigate if delays in resting-state spontaneous fluctuations of the BOLD (sfBOLD) signal can be used to create maps similar to time-to-maximum of the residue function (Tmax) in Moyamoya patients and to determine whether sfBOLD delays affect the results of brain connectivity mapping. MATERIALS AND METHODS: Ten patients were scanned at 3 Tesla using a gradient-echo echo planar imaging sequence for sfBOLD imaging. Cross correlation analysis was performed between each brain voxel signal and a reference signal comprised of either the superior sagittal sinus (SSS) or whole brain (WB) average time course. sfBOLD delay maps were created based on the time shift necessary to maximize the correlation coefficient, and compared with dynamic susceptibility contrast Tmax maps. Standard and time-shifted resting-state BOLD connectivity analyses of the default mode network were compared. RESULTS: Good linear correlations were found between sfBOLD delays and Tmax using the SSS as reference (r(2) = 0.8, slope = 1.4, intercept = -4.6) or WB (r(2) = 0.7, slope = 0.8, intercept = -3.2). New nodes of connectivity were found in delayed regions when accounting for delays in the analysis. CONCLUSION: Resting-state sfBOLD imaging can create delay maps similar to Tmax maps without the use of contrast agents in Moyamoya patients. Accounting for these delays may affect the results of functional connectivity maps.

Dose Reduction in Contrast-Enhanced Cervical MR Angiography: Field Strength Dependency of Vascular Signal Intensity, Contrast Administration, and Arteriographic Quality.

OBJECTIVE: Cervical contrast-enhanced MR angiography (MRA) has proven accurate and superior to noncontrast alternatives. We proposed the systematic investigation of dose reduction in contrast-enhanced MRA, hypothesizing heightened tolerance at 3 T vs 1.5 T. Quantitative and qualitative features were compared between full-dose and 50%-reduced dose examinations at 1.5 T and 3 T. MATERIALS AND METHODS: One hundred eight cervical contrast-enhanced MRA examinations were reviewed for qualitative and quantitative (signal-to-noise ratio [SNR] and contrast-to-noise ratio [CNR]) features across four dose-field strength combinations: 1.5 T, 0.05 mmol/kg; 3 T, 0.05 mmol/kg; 1.5 T, 0.1 mmol/kg; and 3 T, 0.1 mmol/kg. Quantitative features were evaluated among the following segments: aortic arch, common carotid arteries, common carotid bifurcations, and cervical internal carotid arteries. A qualitative visual rating scale was applied for the same segments as well as to the vertebral arteries along their proximal (V1), intraforaminal (V2), and distal extraforaminal (V3) courses. Significant between-group differences were reported at p < 0.05. RESULTS: Qualitatively good arteriography was observed in all segments for all protocols. No significant qualitative differences between protocols were noted throughout evaluation of the anterior cervical circulation. Significant qualitative differences were observed only for V2 and V3 segments at half-dose 1.5-T compared with the remaining protocols (p < 0.05). No significant quantitative differences were present between full-dose and dose-reduced 3-T MRA in any segment. At 1.5 T, significant decrement in SNR and CNR at half-dose was present only within the cervical internal carotid artery. CONCLUSION: Dose reduction in cervical contrast-enhanced MRA is feasible at 3 T without significant compromise in arteriographic quality in most segments. Particularly at 3 T, arteriography is quantitatively and qualitatively robust and may be advisable in high-risk patients.