Spin Labeling Research Articles

Clinical Application Study of 3D-ASL Perfusion Imaging and Magnetic Resonance Diffusion Imaging in Transient Ischemic Attack.

To explore the clinical application of three-dimensional arterial spin labeling (3d-asl) and magnetic resonance diffusion imaging (DWI) in transient ischemic attacks. 40 patients with transient cerebral ischemia in our hospital were selected and included from July 2020 to March 2022. All subjects were detected by DWI and 3D-ASL technology. The positive rate, rCBFand the ROC curve of the two methods in the diagnosis of transient cerebral ischemia were compared; Objective was to compare the relationship between the frequency of transient ischemic attack and hypoperfusion, and vascular stenosis. The 3D-asl examination showed 2 cases of hypoperfusion in the healthy control group (5.00), and the MRI examination showed 4 cases of vascular stenosis in the healthy control group (10.00). The rCBF ratio in the cerebral ischemia group was significantly lower than that in the cerebral ischemia group, which was significantly lower than that in the healthy control group (P < 0.05). The area under the curve (AUC) of 3d-asl in the diagnosis of transient cerebral ischemia was 0.800, and the AUC of DWI in the diagnosis of transient cerebral ischemia was 0.725. The AUC of the combination of the two methods in transient cerebral ischemia was 0.850. There was a significant difference in the attack frequency of patients with transient cerebral ischemia with different perfusion (P < 0.05). There was a significant difference in attack frequency between patients with transient ischemic attack and patients without vascular stenosis (P < 0.05). 3D-asl and DWI technology has higher diagnostic efficiency for transient cerebral ischemia.

The impact of increased cardiac output induced by dobutamine on cerebral blood flow based on MRI 3D-pcASL technology

Objective: To investigate the effect of increased cardiac output induced by dobutamine on cerebral blood flow (CBF) in healthy volunteers using magnetic resonance 3D-pseudo-continuous arterial spin labeling technology. Methods: A prospective study was conducted on 48 healthy volunteers recruited by handy sampling from June 2021 to January 2022. Physiological parameters before (at rest state) and after (under stress state) dobutamine-induced increase in cardiac output were analyzed. Quantitative CBF maps were generated by using arterial spin labeling difference imaging and proton density weighted reference image processing, and CBF changes under the rest and stress states were compared. Multivariable logistic regression model was used to analyze factors associated with reduced CBF. Results: A total of 48 subjects were included, with an age [M (Q1, Q3)] of 25.0 (24.0, 28.0) years, including 43 men and 5 women. Compared with the rest state, the CBF in the anterior cerebral artery [(36.2±6.9) vs (34.5±6.5) ml·(100 g)-1·min-1, P=0.006] and the middle cerebral artery perfusion area [(35.8±6.5) vs (34.1±6.4) ml·(100 g)-1·min-1, P=0.006] decreased under the stress state, however there was no statistically significant change in CBF in the posterior cerebral artery and the vertebral-basilar artery perfusion area (all P>0.05). Logistic regression analysis showed that the decrease in CBF in the anterior cerebral artery and middle cerebral artery supply regions during the stress state were correlated with an increase in diastolic blood pressure [OR (95%CI): 0.887 (0.796-0.989) and 0.895 (0.805-0.994), both P<0.05]. Conclusions: Dobutamine-induced increase in cardiac output leads to a decrease in CBF in anterior cerebral circulation but has no effect on posterior circulation. The increase in diastolic blood pressure is associated with decreased CBF under the stress state. Changes in CBF should be considered in the context of increased cardiac output.

Hypoperfusion of hypothalamic subunits in medication-overuse headache using a 3D PCASL MRI

Hypothalamus is a crucial deep brain area that is responsible for the integration and coordination of various brain functions. The altered perfusion of hypothalamus during headache caused by medication-overuse headache (MOH) was previously unknown. In the current study, the altered perfusion of hypothalamic subregions in MOH patients was investigated using state-of-the-art 3D pseudo-continuous arterial spin labeling (PCASL) MR imaging. In this study, 29 normal controls subjects (NCs) and 29 MOH patients underwent 3D PCASL and brain structural MR imaging. The hypothalamus was automatically segmented into 10 subunits and the volume of each subunit was automatically determined using Freesurfer software (v7.4.1). All segmented hypothalamic subunits were converted to individual hypothalamic subunit masks. The cerebral blood flow (CBF) images were coregistered with the raw brain structural images and resliced. The CBF value of each hypothalamic subunit was extracted from the warped CBF images. The volume and CBF value of each hypothalamic subunit were analyzed using the independent sample T test and Mann–Whitney U test, receiver operating characteristic (ROC) curve analysis, and Pearson and Spearman correlation analysis. Hypothalamic subunits with significantly decreased perfusion were located in the left posterior, left tubular superior, right anterior–inferior, right tubular inferior, right tubular superior, right posterior subunit and the entire right hypothalamus [CBF value for MOH vs NC (mL/100 g·min): 48.41 ± 6.75 vs 54.08 ± 11.47, 44.44 ± 4.79 vs 48.11 ± 7.73, 41.49 (32.90, 61.46) vs 49.38 ± 10.47, 46.62 ± 7.04 vs 53.90 ± 11.75, 42.12 ± 5.74 vs 47.02 ± 9.99, 42.79 ± 5.15 vs 47.93 ± 10.48 and 43.58 ± 5.06 vs 48.65 ± 9.33, respectively] in MOH compared to NC (P < 0.05). ROC analysis for these positive subunits revealed that area under the curve was 0.658–0.693, and ROC curve for left posterior subunit had the highest specificity of 93.10% while the entire right hypothalamus had the highest sensitivity of 72.41%. Further correlation analysis showed that the CBF value of the left posterior, right anterior–inferior, right tubular superior, whole right hypothalamus presented significantly negative correlation with Hamilton Depression Scale (HAMD) score (P < 0.05). Hypoperfusion of hypothalamic subunits may contribute to the understanding of MOH pathogenesis, and the 3D PCASL could be considered as a potential diagnostic and assessment tool for MOH.

Changes of cerebral structure and perfusion in subtypes of systemic sclerosis: a brain magnetic resonance imaging study.

The characteristics of brain impairment in different subtypes of systemic sclerosis (SSc) (dcSSc, diffuse cutaneous SSc; lcSSc, limited cutaneous SSc) remain unclear. This study aimed to characterize cerebral structure and perfusion changes in different subtype of SSc patients using magnetic resonance (MR) imaging. Seventy SSc patients (46.0 ± 11.7 years, 62 females) and 30 healthy volunteers (44.8 ± 13.7 years, 24 females) were recruited and underwent brain MR imaging and Montreal Cognitive Assessment (MoCA) test. Gray matter (GM) volumes were measured using voxel-based morphometry analysis on T1-weighted images. Voxel-based and regional cerebral blood flow (CBF) was calculated on arterial spin labelling images. The cerebral structural and perfusion measurements by MR imaging were compared among dcSSc, lcSSc and healthy subjects using one-way ANOVA. The correlations between clinical characteristics and MR imaging measurements were also analyzed. The dcSSc patients exhibited a significant reduction in GM volume in the para-hippocampal region (cluster p < 0.01, FWE corrected) compared with healthy volunteers. Whereas, SSc patients, particularly lcSSc patients, showed elevated CBF in cerebellum, insula, cerebral cortex, and subcortical structures (regional analyses: all p < 0.05; voxel-based analyses: cluster p < 0.01, FWE corrected). Furthermore, clinical characteristics of modified Rodnan skin score (mRSS) (r value ranged from -0.29 to -0.45), MoCA scores (r = 0.40) and antinuclear antibody (ANA) positivity (r=-0.33) were significantly associated with CBF in some regions (all p < 0.05). The manifestations of brain involvement vary among different subtypes of SSc. In addition, severe skin sclerosis may indicate higher risk of brain involvement in SSc patients.

Dynamic protein-protein interactions of KCNQ1 and KCNE1 measured by EPR line shape analysis

KCNQ1, also known as Kv7.1, is a voltage gated potassium channel that associates with the KCNE protein family. Mutations in this protein has been found to cause a variety of diseases including Long QT syndrome, a type of cardiac arrhythmia where the QT interval observed on an electrocardiogram is longer than normal. This condition is often aggravated during strenuous exercise and can cause fainting spells or sudden death. KCNE1 is an ancillary protein that interacts with KCNQ1 in the membrane at varying molar ratios. This interaction allows for the flow of potassium ions to be modulated to facilitate repolarization of the heart. The interaction between these two proteins has been studied previously with cysteine crosslinking and electrophysiology. In this study, electron paramagnetic resonance (EPR) spectroscopy line shape analysis in tandem with site directed spin labeling (SDSL) was used to observe changes in side chain dynamics as KCNE1 interacts with KCNQ1. KCNE1 was labeled at different sites that were found to interact with KCNQ1 based on previous literature, along with sites outside of that range as a control. Once labeled KCNE1 was incorporated into vesicles, KCNQ1 (helices S1-S6) was titrated into the vesicles. The line shape differences observed upon addition of KCNQ1 are indicative of an interaction between the two proteins. This method provides a first look at the interactions between KCNE1 and KCNQ1 from a dynamics perspective using the full transmembrane portion of KCNQ1.

Supra-tentorial Ependymomas with ZFTA Fusion, YAP1 Fusion, and Astroblastomas, MN1-altered: Characteristic Imaging Features.

Supratentorial (ST) ependymoma subgroups are defined by two different fusions with different prognoses. Astroblastomas, MN1-altered, have ependymal-like histopathologic features and represent adifferential diagnosis in children. We hypothesized that ZFTA-fused ependymoma and YAP1-fused ependymoma on the one hand, and astroblastoma, MN1-altered, on the other hand, show different MRI characteristics. We retrospectively analyzed the preoperative imaging of 45patients with ST ependymoma or astroblastoma between January 2000 and September 2020, blinded to histomolecular grouping. Several characteristics, such as location, tumor volume, calcifications, solid/cystic component, and signal enhancement or diffusion were evaluated. We compared imaging characteristics according to their molecular subtype (ZFTA-fused, YAP1-fused, and astroblastoma, MN1-altered). Thirty-nine patients were classified as having an ependymoma, 35with aZFTA fusion and four with aYAP1 fusion, and six as having an astroblastoma, MN1-altered. YAP1-fused ependymomas were more likely to involve at least 3lobes than ZFTA-fused ependymomas. Astroblastomas were located in the frontal lobe in 100% of the tumors versus 49% of the ependymomas. Cerebral blood flow by arterial spin labeling was higher in astroblastomas than in ependymomas. There were no differences in the other characteristics between the molecular groups. All the tumors showed common features: intra-axial extra-ventricular tumors, very frequent contrast enhancement (39/43, 91%), acystic/necrotic component (41/45, 91%), restricted diffusion (32/36, 89%), calcifications (15/18, 83%), and peri-tumoral edema (38/44, 86%). The distinction between ST ependymoma subtypes and astroblastomas can be guided by several imaging features. These tumors share common imaging features that may help to differentiate ST ependymomas and astroblastomas from other pediatric ST tumors.

Three-dimensional pseudocontinuous arterial spin labeling with dual postlabeling delay for reflecting cerebral blood flow regulation in patients with hydrocephalus: a retrospective cross-sectional study.

Three-dimensional pseudo-continuous arterial spin-labeling (3D pCASL) with dual postlabeling delay (PLD) captures both early and delayed cerebral blood flow (CBF), yet its potential in reflecting blood flow regulation in hydrocephalus patients remains uncertain. This study investigated the hemodynamic characteristics in patients with hydrocephalus and whether the difference in cerebral blood flow using short and long PLDs (ΔCBF = CBFPLD =2.5 s - CBFPLD =1.5 s) could reflect cerebral regulation and further aimed to demonstrate the associations between regional ΔCBF and the degree of ventricular dilatation. This retrospective study included consecutive patients with hydrocephalus and control participants attending The Second Affiliated Hospital of Nanchang University from December 2017 to December 2022. The CBF in 18 brain regions was manually delineated by two radiologists. Regional CBF and ΔCBF were compared via covariance analyses. The associations between ΔCBF and the degree of ventricular dilatation were investigated using linear regression analyses and interaction analysis. In total, 58 patients with communicating hydrocephalus, 57 patients with obstructive hydrocephalus, and 52 controls were analyzed. CBF of the hydrocephalus groups was lower than that of the control group at the shorter PLD. CBF was higher at a longer PLD, with no difference between the hydrocephalus groups and the control group in some regions. The hydrocephalus groups showed a higher ΔCBF compared to the control group. Furthermore, in the left medial watershed (10.6±5.66 vs. 7.01±5.88 mL/100 g/min; P=0.038), communicating hydrocephalus exhibited greater ΔCBF than did obstructive hydrocephalus. ΔCBF of the right posterior external watershed [adjusted β: 0.276; 95% confidence interval (CI): 0.047-0.505; P=0.019] and right parietal cortex (adjusted β: 0.277; 95% CI: 0.056-0.498; P=0.015) in the obstructive hydrocephalus group and ΔCBF of the left internal watershed (adjusted β: 0.274; 95% CI: 0.013-0.536; P=0.040) in the communicating hydrocephalus group were associated with the degree of ventricular dilatation, respectively. Patients with hydrocephalus showed cerebral regulation in maintaining adequate CBF, resulting in longer arterial transit times. The ability to regulate CBF in brain regions represented by the watershed was associated with the degree of ventricular dilation.

Multiparametric simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) incorporating intratumoral and peritumoral regions for grading of glioma.

Preoperative grading gliomas is essential for therapeutic clinical decision-making. Current non-invasive imaging modality for glioma grading were primarily focused on magnetic resonance imaging (MRI) or positron emission tomography (PET) of the tumor region. However, these methods overlook the peritumoral region (PTR) of tumor and cannot take full advantage of the biological information derived from hybrid-imaging. Therefore, we aimed to combine multiparameter from hybrid 18F-fluorodeoxyglucose (18F-FDG) PET/MRI of the solid component and PTR were combined for differentiating high-grade glioma (HGG) from low-grade glioma (LGG). A total of 76 patients with pathologically confirmed glioma (41 HGG and 35 LGG) who underwent simultaneous 18F-FDG PET, arterial spin labelling (ASL), and diffusion-weighted imaging (DWI) with hybrid PET/MRI were retrospectively enrolled. The relative maximum standardized uptake value (rSUVmax), relative cerebral blood flow (rCBF), and relative minimum apparent diffusion coefficient (rADCmin) for the solid component and PTR at different distances outside tumoral border were compared. Receiver operating characteristic (ROC) curves were applied to assess the grading performance. A nomogram for HGG prediction was constructed. HGGs displayed higher rSUVmax and rCBF but lower rADCmin in the solid component and 5 mm-adjacent PTR, lower rADCmin in 10 mm-adjacent PTR, and higher rCBF in 15- and 20-mm-adjacent PTR. rSUVmax in solid component performed best [area under the curve (AUC) =0.865] as a single parameter for grading. Combination of rSUVmax in the solid component and adjacent 20 mm performed better (AUC =0.881). Integration of all 3 indicators in the solid component and adjacent 20 mm performed the best (AUC =0.928). The nomogram including rSUVmax, rCBF, and rADCmin in the solid component and 5-mm-adjacent PTR predicted HGG with a concordance index (C-index) of 0.906. Multiparametric 18F-FDG PET/MRI from the solid component and PTR performed excellently in differentiating HGGs from LGGs. It can be used as a non-invasive and effective tool for preoperative grade stratification of patients with glioma, and can be considered in clinical practice.

Preliminary investigations into human neurofluid transport using multiple novel non-contrast MRI methods.

We discuss two potential non-invasive MRI methods to study phenomena related to subarachnoid cerebrospinal fluid (CSF) motion and perivascular fluid transport, and their association with sleep and aging. We apply diffusion-based intravoxel incoherent motion (IVIM) imaging to evaluate pseudodiffusion coefficient, D*, or CSF movement across large spaces like the subarachnoid space (SAS). We also performed perfusion-based multi-echo, Hadamard encoded arterial spin labeling (ASL) to evaluate whole brain cortical cerebral blood flow (CBF) and trans-endothelial exchange (Tex) of water from the vasculature into the perivascular space and parenchyma. Both methods were used in young adults (N = 9, 6 F, 23 ± 3 years old) in the setting of sleep and sleep deprivation. To study aging, 10 older adults (6 F, 67 ± 3 years old) were imaged after a night of normal sleep and compared with the young adults. D* in SAS was significantly (p < 0.05) reduced with sleep deprivation (0.016 ± 0.001 mm2/s) compared to normal sleep (0.018 ± 0.001 mm2/s) and marginally reduced with aging (0.017 ± 0.001 mm2/s, p = 0.029). Cortical CBF and Tex were unchanged with sleep deprivation but significantly lower in older adults (37 ± 3 ml/100 g/min, 578 ± 61 ms) than in young adults (42 ± 2 ml/100 g/min, 696 ± 62 ms). IVIM was sensitive to sleep physiology and aging, and multi-echo, multi-delay ASL was sensitive to aging.

Spatial coefficient of variation of arterial spin labeling magnetic resonance imaging can predict decreased cerebrovascular reactivity measured by acetazolamide challenge single-photon emission tomography.

The aim of this study was to investigate whether the spatial coefficient of variation of arterial spin labeling (ASL-CoV) acquired in clinical settings can be used to estimate decreased cerebrovascular reactivity (CVR) measured with single-photon emission computed tomography (SPECT) and acetazolamide challenge in patients with atherosclerotic stenosis of intra- or extracranial arteries. We evaluated the data of 27 atherosclerotic stenosis patients who underwent pseudocontinuous ASL and SPECT. After spatial normalization, regional values were measured using the distributed middle cerebral artery territorial atlas of each patient. We performed comparisons, correlations, and receiver operating characteristic (ROC) curve analyses between ASL-cerebral blood blow (CBF), ASL-CoV, SPECT-CBF and SPECT-CVR. Although the ASL-CBF values were positively correlated with SPECT-CBF values (r = 0.48, 95% confidence interval (CI) = 0.28-0.64), no significant difference in ASL-CBF values was detected between regions with and without decreased CVR. However, regions with decreased CVR had significantly greater ASL-CoV values than regions without decreased CVR. SPECT-CVR was negatively correlated with ASL-CoV (ρ = -0.29, 95% CI = -0.49 - -0.06). The area under the ROC curve of ASL-CoV in predicting decreased CVR (0.66, 95% CI = 0.51-0.81) was greater than that of ASL-CBF (0.51, 95% CI = 0.34-0.68). An ASL-CoV threshold value of 42% achieved a high specificity of 0.93 (sensitivity = 0.42, positive predictive value = 0.77, and negative predictive value = 0.75). ASL-CoV acquired by single postlabeling delay without an acetazolamide challenge may aid in the identification of patients with decreased CVR on SPECT.

Pulsed Dipolar EPR for Self-Limited Complexes of Oligonucleotides Studies.

Pulsed electron-electron double resonance (PELDOR) spectroscopy is a powerful method for determining nucleic acid (NA) structure and conformational dynamics. PELDOR with molecular dynamics (MD) simulations opens up unique possibilities for defining the conformational ensembles of flexible, three-dimensional, self-assembled complexes of NA. Understanding the diversity and structure of these complexes is vital for uncovering matrix and regulative biological processes in the human body and artificially influencing them for therapeutic purposes. To explore the reliability of PELDOR and MD simulations, we site-specifically attached nitroxide spin labels to oligonucleotides, which form self-assembled complexes between NA chains and exhibit significant conformational flexibility. The DNA complexes assembled from a pair of oligonucleotides with different linker sizes showed excellent agreement between the distance distributions obtained from PELDOR and calculated from MD simulations, both for the mean inter-spin distance and the distance distribution width. These results prove that PELDOR with MD simulations has significant potential for studying the structure and dynamics of conformational flexible complexes of NA.

Non-contrast MR angiography: physical principles and clinical applications in chest, abdomen and pelvis imaging.

This review article focuses on the advancements in non-contrast magnetic resonance angiography (NC-MRA) and its increasing importance in body imaging, especially for patients with renal complications, pregnant women, and children. It highlights the relevance of NC-MRA in chest, abdominal, and pelvis imaging and details various bright-blood NC-MRA techniques like cardiac-gated 3D Fast Spin Echo (FSE), balanced Steady-State Free Precession (bSSFP), Arterial Spin Labeling (ASL), and 4D flow methods. The article explains the operational principles of these techniques, their clinical applications, and their advantages over traditional contrast-enhanced methods. Special attention is given to the utility of these techniques in diverse imaging scenarios, including liver, renal, and pelvic imaging. The article underscores the growing importance of NC-MRA in medical diagnostics, offering insights into current practices and potential future developments. This comprehensive review is a valuable resource for radiologists and clinicians, emphasizing NC-MRA's role in enhancing patient care and diagnostic accuracy across various medical conditions.

A multi-task generative model for simultaneous post-contrast MR image synthesis and brainstem glioma segmentation

ObjectivesThis study aims to generate post-contrast MR images reducing the exposure of gadolinium-based contrast agents (GBCAs) for brainstem glioma (BSG) detection, simultaneously delineating the BSG lesion, and providing high-resolution contrast information. MethodsA retrospective cohort of 30 patients diagnosed with brainstem glioma was included. Multi-contrast images, including pre-contrast T1 weighted (pre-T1w), T2 weighted (T2w), arterial spin labeling (ASL) and post-contrast T1w images, were collected. A multi-task generative model was developed to synthesize post-contrast T1w images and simultaneously segment BSG masks from the multi-contrast inputs. Performance evaluation was conducted using peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and mean absolute error (MAE) metrics. A perceptual study was also undertaken to assess diagnostic quality. ResultsThe proposed model achieved SSIM of 0.86 ± 0.04, PSNR of 26.33 ± 0.05 and MAE of 57.20 ± 20.50 for post-contrast T1w image synthesis. Automated delineation of the BSG lesions achieved Dice similarity coefficient (DSC) score of 0.88 ± 0.27. ConclusionsThe proposed model can synthesize high-quality post-contrast T1w images and accurately segment the BSG region, yielding satisfactory DSC scores. Clinical relevance statementThe synthesized post-contrast MR image presented in this study has the potential to reduce the usage of gadolinium-based contrast agents, which may pose risks to patients. Moreover, the automated segmentation method proposed in this paper aids radiologists in accurately identifying the brainstem glioma lesion, facilitating the diagnostic process.

Reduced B0/B1 + sensitivity in velocity-selective inversion arterial spin labeling using adiabatic refocusing pulses.

To mitigate the B0/B1 + sensitivity of velocity-selective inversion (VSI) pulse trains for velocity-selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact-free VSI-based perfusion imaging through single-pair label-control subtractions, reducing the need for the currently required four-pair dynamic phase-cycling (DPC) technique when using a velocity-insensitive control. We introduce a Fourier-transform VSI (FT-VSI) train that incorporates sinc-modulated hard excitation pulses with MLEV-8-modulated adiabatic hyperbolic secant refocusing pairs. We compare performance between this train and the standard composite refocusing train, including with and without DPC, for dual-module VSI VSASL. We evaluate (1) simulated velocity-selective profiles and subtraction fidelity across a broad B0/B1 + range, (2) subtraction fidelity in phantoms, and (3) image quality, artifact presence, and gray-matter perfusion heterogeneity (as measured by the spatial coefficient of variation) in healthy human subjects. Adiabatic refocusing significantly improves FT-VSI robustness to B0/B1 + inhomogeneity for a single label-control subtraction. Subtraction fidelity is dramatically improved in both simulation and phantoms compared with composite refocusing without DPC, and is similar compared with DPC methods. In humans, marked artifacts seen with the non-DPC composite refocusing approach are eliminated, corroborated by significantly reduced gray-matter heterogeneity (via lower spatial coefficient of variation values). A novel VSASL labeling train using adiabatic refocusing pulses for VSI was found to reduce artifacts related to B0/B1 + inhomogeneity, thereby providing an alternative to DPC and its associated limitations, which include increased vulnerability to physiological noise and motion, reduced functional MRI applicability, and suboptimal data censoring.

Cerebral blood flow in relation to peripheral endothelial function in youth bipolar disorder

IntroductionAnomalous cerebral blood flow (CBF) is evident in bipolar disorder (BD), however the extent to which CBF reflects peripheral vascular function in BD is unknown. This study investigated endothelial function, an index of early atherosclerosis and cardiovascular disease risk, in relation to CBF among youth with BD. MethodsParticipants included 113 youth, 13–20 years old (66 BD; 47 healthy controls [HC]). CBF was measured using arterial spin labeling with 3T MRI. Region of interest analyses (ROI; global grey matter, middle frontal gyrus, anterior cingulate cortex, temporal cortex, caudate) were undertaken alongside voxel-wise analyses. Reactive hyperemia index (RHI), a measure of endothelial function, was assessed non-invasively via pulse amplitude tonometry. General linear models were used to examine RHI and RHI-by-diagnosis associations with CBF, controlling for age, sex, and body mass index. Bonferroni correction for multiple comparisons was used for ROI analyses, such that the significance level was divided by the number of ROIs (α = 0.05/5 = 0.01). Cluster-extent thresholding was used to correct for multiple comparisons for voxel-wise analyses. ResultsROI findings were not significant after correction. Voxel-wise analyses found that higher RHI was associated with lower left thalamus CBF in the whole group (p < 0.001). Additionally, significant RHI-by-diagnosis associations with CBF were found in three clusters: left intracalcarine cortex (p < 0.001), left thalamus (p < 0.001), and right frontal pole (p = 0.006). Post-hoc analyses showed that in each cluster, higher RHI was associated with lower CBF in BD, but higher CBF in HC. ConclusionWe found that RHI was differentially associated with CBF in youth with BD versus HC. The unanticipated association of higher RHI with lower CBF in BD could potentially reflect a compensatory mechanism. Future research, including prospective studies and experimental designs are warranted to build on the current findings.

Quantitative transport mapping of multi-delay arterial spin labeling MRI detects early blood perfusion alterations in Alzheimer’s disease

BackgroundQuantitative transport mapping (QTM) of blood velocity, based on the transport equation has been demonstrated higher accuracy and sensitivity of perfusion quantification than the traditional Kety’s method-based cerebral blood flow (CBF). This study aimed to investigate the associations between QTM velocity and cognitive function in Alzheimer’s disease (AD) using multiple post-labeling delay arterial spin labeling (ASL) MRI.MethodsA total of 128 subjects (21 normal controls (NC), 80 patients with mild cognitive impairment (MCI), and 27 AD) were recruited prospectively. All participants underwent MRI examination and neuropsychological evaluation. QTM velocity and traditional CBF maps were computed from multiple delay ASL. Regional quantitative perfusion measurements were performed and compared to study group differences. We tested the hypothesis that cognition declines with reduced cerebral blood perfusion with consideration of age and gender effects.ResultsIn cortical gray matter (GM) and the hippocampus, QTM velocity and CBF showed decreased values in the AD group compared to NC and MCI groups; QTM velocity, but not CBF, showed a significant difference between MCI and NC groups. QTM velocity and CBF showed values decreasing with age; QTM velocity, but not CBF, showed a significant gender difference between male and female. QTM velocity and CBF in the hippocampus were positively correlated with cognition, including global cognition, memory, executive function, and language function.ConclusionThis study demonstrated an increased sensitivity of QTM velocity as compared with the traditional Kety’s method-based CBF. Specifically, we observed only in QTM velocity, reduced perfusion velocity in GM and the hippocampus in MCI compared with NC. Both QTM velocity and CBF demonstrated a reduction in AD vs. controls. Decreased QTM velocity and CBF in the hippocampus were correlated with poor cognitive measures. These findings suggest QTM velocity as potential biomarker for early AD blood perfusion alterations and it could provide an avenue for early intervention of AD.

Assessment of resting cerebral perfusion between methamphetamine-associated psychosis and schizophrenia through arterial spin labeling MRI.

The clinical manifestations of methamphetamine (METH)-associated psychosis (MAP) and acute paranoid schizophrenia (SCZ) are similar. This study aims to assess regional cerebral blood flow (rCBF) in individuals who use METH and in those with SCZ using the MRI arterial spin labeling (ASL) technique. We prospectively recruited 68 participants and divided them into four groups: MAP (N = 15), SCZ (N = 13), METH users with no psychosis (MNP; N = 22), and normal healthy controls (CRL; N = 18). We measured rCBF using an MRI three-dimensional pseudo-continuous ASL sequence. Clinical variables were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS). Group-level rCBF differences were analyzed using a two-sample t-test. Decreased rCBF was found in the precuneus, premotor cortex, caudate nucleus, dorsolateral prefrontal cortex, and thalamus in the MNP group compared with the CRL group. The MAP group had significantly decreased rCBF in the precuneus, hippocampus, anterior insula, inferior temporal gyrus, inferior orbitofrontal gyrus, and superior occipital gyrus compared with the MNP group. Increased rCBF in the precuneus and premotor cortex was seen in the MAP group compared with the SCZ group. rCBF in the precuneus and premotor cortex significantly correlated negatively with the PANSS but correlated positively with BACS scores in the MAP and SCZ groups. METH exposure was associated with decreased rCBF in the precuneus and premotor cortex. Patients with MAP exhibited higher rCBF than those with SCZ, implying preserved insight and favorable outcomes. rCBF can therefore potentially serve as a diagnostic approach to differentiate patients with MAP from those with SCZ.

Rate of abnormalities in quantitative MR neuroimaging of persons with chronic traumatic brain injury

BackgroundMild traumatic brain injury (mTBI) can result in lasting brain damage that is often too subtle to detect by qualitative visual inspection on conventional MR imaging. Although a number of FDA-cleared MR neuroimaging tools have demonstrated changes associated with mTBI, they are still under-utilized in clinical practice.MethodsWe investigated a group of 65 individuals with predominantly mTBI (60 mTBI, 48 due to motor-vehicle collision, mean age 47 ± 13 years, 27 men and 38 women) with MR neuroimaging performed in a median of 37 months post-injury. We evaluated abnormalities in brain volumetry including analysis of left-right asymmetry by quantitative volumetric analysis, cerebral perfusion by pseudo-continuous arterial spin labeling (PCASL), white matter microstructure by diffusion tensor imaging (DTI), and neurometabolites via magnetic resonance spectroscopy (MRS).ResultsAll participants demonstrated atrophy in at least one lobar structure or increased lateral ventricular volume. The globus pallidi and cerebellar grey matter were most likely to demonstrate atrophy and asymmetry. Perfusion imaging revealed significant reductions of cerebral blood flow in both occipital and right frontoparietal regions. Diffusion abnormalities were relatively less common though a subset analysis of participants with higher resolution DTI demonstrated additional abnormalities. All participants showed abnormal levels on at least one brain metabolite, most commonly in choline and N-acetylaspartate.ConclusionWe demonstrate the presence of coup-contrecoup perfusion injury patterns, widespread atrophy, regional brain volume asymmetry, and metabolic aberrations as sensitive markers of chronic mTBI sequelae. Our findings expand the historic focus on quantitative imaging of mTBI with DTI by highlighting the complementary importance of volumetry, arterial spin labeling perfusion and magnetic resonance spectroscopy neurometabolite analyses in the evaluation of chronic mTBI.

Probing conformational dynamics of DNA binding by CO-sensing transcription factor, CooA

The transcription factor CooA is a CRP/FNR (cAMP receptor protein/ fumarate and nitrate reductase) superfamily protein that uses heme to sense carbon monoxide (CO). Allosteric activation of CooA in response to CO binding is currently described as a series of discrete structural changes, without much consideration for the potential role of protein dynamics in the process of DNA binding. This work uses site-directed spin-label electron paramagnetic resonance spectroscopy (SDSL-EPR) to probe slow timescale (μs-ms) conformational dynamics of CooA with a redox-stable nitroxide spin label, and IR spectroscopy to probe the environment at the CO-bound heme. A series of cysteine substitution variants were created to selectively label CooA in key functional regions, the heme-binding domain, the 4/5-loop, the hinge region, and the DNA binding domain. The EPR spectra of labeled CooA variants are compared across three functional states: Fe(III) “locked off”, Fe(II)-CO “on”, and Fe(II)-CO bound to DNA. We observe changes in the multicomponent EPR spectra at each location; most notably in the hinge region and DNA binding domain, broadening the description of the CooA allosteric mechanism to include the role of protein dynamics in DNA binding. DNA-dependent changes in IR vibrational frequency and band broadening further suggest that there is conformational heterogeneity in the active WT protein and that DNA binding alters the environment of the heme-bound CO.

Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression

BackgroundMajor depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin’s acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression.MethodsFifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures.DiscussionThis study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin’s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response.Trial registrationClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.