Biology subjects

Bibic, A.

Publications and source records attributed to Bibic, A..

6 recordsLinked to original sources

bioRxiv2026

Dissociation of Diffusion and Perfusion Responses After Intracerebral Hemorrhage

Background and PurposeIntracerebral hemorrhage (ICH) triggers complex secondary injury processes that extend beyond hematoma formation. While structural and diffusion MRI are widely used to characterize tissue injury, the spatiotemporal evolution of cerebral perfusion after ICH, particularly in small-animal models, remains poorly defined. Here, we performed a longitudinal multiparametric MRI study to delineate the relationship between microstructural injury and cerebral perfusion following experimental ICH. MethodsA collagenase-induced mouse model of ICH was studied longitudinally from baseline to 21 days post-stroke. Hematoma volume, tissue microstructure, and cerebral blood perfusion (CBP) were quantified using T2*-weighted MRI, diffusion-weighted imaging, and pseudo-continuous arterial spin labeling (pCASL) MRI, respectively. Apparent diffusion coefficient (ADC) and CBP were quantified in multiple brain regions from both ipsilateral and contralateral hemispheres and analyzed using linear mixed-effects models. ResultsHematoma volume peaked acutely and gradually attenuated over time. ADC exhibited an early reduction largely confined to the striatum, followed by progressive recovery, consistent with localized cytotoxic edema and subsequent attenuation. In contrast, CBP showed a marked bilateral hypoperfusion during the acute phase, followed by a delayed perfusion increase that was spatially restricted to the ipsilateral striatum. Notably, significant contralateral perfusion alterations were observed despite minimal contralateral diffusion changes, indicating a dissociation between microstructural injury and vascular regulation. ConclusionsMicrostructural and perfusion responses after ICH follow distinct spatiotemporal trajectories. Whereas diffusion abnormalities are largely localized to the hemorrhagic core, perfusion disturbances extend bilaterally beyond the lesion site. These findings challenge the common assumption of contralateral physiological stability after focal hemorrhage and highlight the value of quantitative perfusion MRI for capturing systemic cerebrovascular responses that are not reflected by diffusion or anatomical measures alone.

physiology↗

bioRxiv2025

Vascular Microbleeds Without Brain Atrophy: A Microvascular Signature of Mid-Stage 5xFAD Pathology

Cerebral microbleeds are increasingly recognized as a downstream manifestation of vascular injury in Alzheimers disease (AD), arising secondary to cerebral amyloid angiopathy (CAA). Here, we examined the pathological specificity of microbleeds by comparing an amyloidosis mouse model (5xFAD) with a small-vessel disease (SVD) model characterized by vascular smooth-muscle cell loss. In vivo multimodal MRI, including gradient-echo, spin-echo, and diffusion-weighted imaging, was complemented by ex vivo high-resolution anatomical scans for validation. Both in vivo and ex vivo gradient-echo MRI consistently revealed hippocampal microbleeds in the 5xFAD model without macroscopic atrophy or ventricular enlargement, whereas no microbleeds or blood-brain barrier disruption were detected in the SVD model. Diffusion-weighted MRI further showed region-specific alterations in apparent diffusion coefficient within the midbrain of 5xFAD mice, but not in other regions or in the SVD cohort. These findings indicate that microbleeds are a pathology-specific marker of amyloid-related vascular injury. The imaging evidence underscores the potential of microbleeds as a disease-specific biomarker for detecting amyloid-driven vascular fragility and refining diagnostic and therapeutic strategies for AD.

neuroscience↗

bioRxiv2025

Hyperintense signals in cerebral blood flow maps acquired with pseudo-continuous arterial spin labeling MRI in mice

Background and PurposePseudo-continuous arterial spin labeling (pCASL) MRI is a widely used, noninvasive, contrast-agent-free technique for measuring cerebral blood flow (CBF) and assessing vascular dysfunction across diverse clinical settings and murine disease models. In practice, arterial-transit artifacts that generate hyperintense signal in CBF maps warrant careful consideration. While these effects are well characterized in humans, they are less well understood in mice owing to the marked interspecies physiological differences. MethodsTo address this knowledge gap, we systematically characterized pCASL hyperintense signal as a function of post-labeling delay (PLD) and crusher-gradient strength in mice. Numerical simulations were also performed to validate the experimental findings. ResultsWe found that hyperintense signals in mice extend to arteries, major veins, and ventricular structures (e.g., choroid plexus). Such a pattern was different from human pCASL images, where hyperintense signals are predominantly present in arteries. Statistical analyses supported a PLD of 500 ms as a pragmatic balance between detection sensitivity and suppression of vascular contamination. Additional experiments and numerical simulations showed that, within the tested range, stronger crusher gradients provided little extra vascular suppression--primarily because large vessel calibers relative to small voxels limit intravoxel phase dispersion. These findings refine the interpretation of murine pCASL signals and facilitate more accurate perfusion imaging in preclinical pathophysiological studies.

bioengineering↗

bioRxiv2025

Vascular smooth muscle cell loss, but not neuroinflammation, drives cerebrovascular reactivity impairment in Alzheimer disease

INTRODUCTIONCerebrovascular reactivity (CVR) impairment is a key feature of Alzheimers disease (AD), but its mechanistic basis remains unclear. This study examined whether vascular smooth muscle cell (VSMC) loss, rather than amyloidosis or neuroinflammation, underlies CVR deficits. METHODSNon-contrast MRI, including phase-contrast and pseudo-continuous arterial spin labeling, was performed in mouse models of amyloidosis (5xFAD), VSMC degeneration (CADASIL), and lipopolysaccharide-induced neuroinflammation. Characterization of vascular, amyloid-{beta}, and inflammatory markers were performed for pathological assessment. RESULTSCVR impairment emerged only when VSMC loss was present in CADASIL mice and at older ages in 5xFAD mice (9-12 months). Amyloid-{beta} deposition occurred earlier than VSMC loss or CVR decline. Neuroinflammation primarily altered baseline cerebral blood flow without affecting CVR or VSMC integrity. DISCUSSIONThese findings identify VSMC degeneration as an important driver of CVR impairment independent of cerebral amyloid angiopathy or inflammation, highlighting vascular integrity as a potential therapeutic target in AD. HighlightsO_LICerebrovascular reactivity (CVR) impairment occurred in 5xFAD mice only when vascular smooth muscle cell (VSMC) loss was present C_LIO_LI5xFAD mice exhibited prominent parenchymal but minimal vascular amyloid-{beta} deposition C_LIO_LIVSMC developmental deficiency resulted in CVR impairment in a small-vessel disease (SVD) model C_LIO_LINeuroinflammation primarily altered baseline cerebral blood flow (CBF) without affecting CVR C_LI

bioengineering↗

bioRxiv2025

Improved Injury Detection Through Harmonizing Multi-Site Neuroimaging Data after Experimental TBI: A Translational Outcomes Project in NeuroTrauma (TOP-NT) Consortium Study

Multi-site neuroimaging studies have become increasingly common in order to generate larger samples of reproducible data to answer questions associated with smaller effect sizes. The data harmonization model NeuroCombat has been shown to remove site effects introduced by differences in site-related technical variance while maintaining group differences, yet its effect on improving statistical power in pre-clinical models of CNS disease is unclear. The present study examined fractional anisotropy data computed from diffusion weighted imaging data at 3 and 30 days post-controlled cortical impact injury from 184 adult rats across four sites as part of the Translational-Outcome-Project-in-Neurotrauma (TOP-NT) Consortium. Findings confirmed prior clinical reports that NeuroCombat fails to remove site effects in data containing a high proportion-of-outliers (>5%) and skewness, which introduced significant variation in non-outlier sites. After removal of one outlier site and harmonization using a global sham population, harmonization displayed an increase in effect size in data that displayed group level effects (p<0.01) in both univariate and voxel-level volumes of pathology. This was characterized by movement toward similar distributions in voxel measurements (Kolmogorov-Smirnov p<<0.001 to >0.01) and statistical power increases within the ipsilateral cortex. Harmonization improved statistical power and frequency of significant differences in areas with existing group differences, thus improving the ability to detect regions affected by injury rather than by other confounds. These findings indicate the utility of NeuroCombat in reproducible data collection, where biological differences can be accurately revealed to allow for greater reliability in multi-site neuroimaging studies. Significance StatementThis project demonstrates the utility of NeuroCombat in reducing site effects in multi-site rodent imaging. We also demonstrate that harmonization improves the ability to distinguish between sham and injured rats at the voxel level and increase statistical power and effect size in areas of injury. Multi-center studies are becoming more common to allow for increased efficiency in data collection, and with conservative approaches and analysis into the datasets, NeuroCombat can be utilized to improve study reliability and reproducibility.

neuroscience↗

bioRxiv2025

Bidirectional crusher gradient method for estimating the labeling efficiency of pseudo-continuous arterial spin labeling MRI in mice

Pseudo-continuous arterial spin labeling (pCASL) MRI is a widely used imaging technique for studying brain perfusion in health and disease due to its non-invasive and non-contrast nature. Accurate quantification of absolute perfusion values from pCASL signals requires the knowledge of labeling efficiency. However, to date, a reliable technique to measure pCASL labeling efficiency has not been available. In this study, we propose a method using bidirectional crusher gradients to modulate vascular signals in the azygos pericallosal artery (azPA) of the mouse brain, applied with and without pCASL labeling. The combination of corresponding signals allows the estimation of labeling efficiency. Upon systematic testing, optimal acquisition parameters included a labeling duration [≥] 1170 ms, a repetition time of 3 seconds, and an imaging slice thickness of 0.75 mm. In order to quantitatively estimate labeling efficiency, the bolus arrival time to azPA is required and found to be 218.7 +/- 13.3 ms. Typical labeling efficiencies in mouse pCASL scans were 0.780 +/- 0.048 (mean +/- standard deviation). Furthermore, faster arterial flow induced by hypercapnia was found to increase pCASL labeling efficiency. Our method can improve the accuracy of pCASL quantification in mice, offering great potential for advancing its applications in pathophysiological studies.

neuroscience↗