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1.
Brain Imaging Behav ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235695

RESUMEN

Resting state correlations between blood oxygenation level dependent (BOLD) MRI signals from voxels in white matter (WM) are demonstrably anisotropic, so that functional correlation tensors (FCT) may be used to quantify the underlying microstructure of BOLD effects in WM tracts. However, the overall spatial distribution of FCTs and their metrics in specific populations has not yet been established, and the factors that affect their precise arrangements remain unclear. Changes in WM occur with normal aging, and these may be expected to affect FCTs. We hypothesized that FCTs exhibit a characteristic spatial pattern and may show systematic changes with aging or other factors. Here we report our analyses of the FCT characteristics of fMRI images of a large cohort of 461 cognitively normal subjects (190 females, 271 males) sourced from the Open Access Series of Imaging Studies (OASIS), with age distributions of 42 y/o - 95 y/o. Group averages and statistics of FCT indices, including axial functional correlations, radial functional correlations, mean functional correlations and fractional anisotropy, were quantified in WM bundles defined by the JHU ICBM-DTI-81 WM atlas. In addition, their variations with normal aging were examined. The results revealed a dimorphic distribution of changes in FCT metrics with age, with decreases of the functional correlations in some regions and increases in others. Supplementary analysis revealed that females exhibited significant age effects on a greater number of WM areas, but the interaction between age and sex was not significant. The findings demonstrate the reproducibility of the spatial distribution of FCT metrics and reveal subtle regional changes with age.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39220214

RESUMEN

White matter signals in resting state blood oxygen level dependent functional magnetic resonance (BOLD-fMRI) have been largely discounted, yet there is growing evidence that these signals are indicative of brain activity. Understanding how these white matter signals capture function can provide insight into brain physiology. Moreover, functional signals could potentially be used as early markers for neurological changes, such as in Alzheimer's Disease. To investigate white matter brain networks, we leveraged the OASIS-3 dataset to extract white matter signals from resting state BOLD-FMRI data on 711 subjects. The imaging was longitudinal with a total of 2,026 images. Hierarchical clustering was performed to investigate clusters of voxel-level correlations on the timeseries data. The stability of clusters was measured with the average Dice coefficients on two different cross fold validations. The first validated the stability between scans, and the second validated the stability between populations. Functional clusters at hierarchical levels 4, 9, 13, 18, and 24 had local maximum stability, suggesting better clustered white matter. In comparison with JHU-DTI-SS Type-I Atlas defined regions, clusters at lower hierarchical levels identified well-defined anatomical lobes. At higher hierarchical levels, functional clusters mapped motor and memory functional regions, identifying 50.00%, 20.00%, 27.27%, and 35.14% of the frontal, occipital, parietal, and temporal lobe regions respectively.

3.
J Magn Reson ; 367: 107760, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39241283

RESUMEN

The Kӓrger model and its derivatives have been widely used to incorporate transcytolemmal water exchange rate, an essential characteristic of living cells, into analyses of diffusion MRI (dMRI) signals from tissues. The Kӓrger model consists of two homogeneous exchanging components coupled by an exchange rate constant and assumes measurements are made with sufficiently long diffusion time and slow water exchange. Despite successful applications, it remains unclear whether these assumptions are generally valid for practical dMRI sequences and biological tissues. In particular, barrier-induced restrictions to diffusion produce inhomogeneous magnetization distributions in relatively large-sized compartments such as cancer cells, violating the above assumptions. The effects of this inhomogeneity are usually overlooked. We performed computer simulations to quantify how restriction effects, which in images produce edge enhancements at compartment boundaries, influence different variants of the Kӓrger-model. The results show that the edge enhancement effect will produce larger, time-dependent estimates of exchange rates in e.g., tumors with relatively large cell sizes (>10 µm), resulting in overestimations of water exchange as previously reported. Moreover, stronger diffusion gradients, longer diffusion gradient durations, and larger cell sizes, all cause more pronounced edge enhancement effects. This helps us to better understand the feasibility of the Kärger model in estimating water exchange in different tissue types and provides useful guidance on signal acquisition methods that may mitigate the edge enhancement effect. This work also indicates the need to correct the overestimated transcytolemmal water exchange rates obtained assuming the Kärger-model.


Asunto(s)
Simulación por Computador , Imagen de Difusión por Resonancia Magnética , Agua , Imagen de Difusión por Resonancia Magnética/métodos , Agua/química , Humanos , Algoritmos , Difusión , Modelos Biológicos
4.
Behav Brain Res ; 476: 115265, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307286

RESUMEN

We have previously demonstrated that machine learning-based video analysis, conducted via DeepLabCut, is more sensitive for detecting subtle deficits in hand grasping behavior than traditional end-point performance assessments. This superiority was observed in a nonhuman primate (NHP) model of cervical spinal cord injury, specifically a dorsal column lesion (DCL). The current study aims to further characterize the kinematic aspects of the deficits in hand reaching, grasping, and retrieving behavior from a 3D perspective following a DCL. Squirrel monkeys were trained to retrieve sugar pellets from eight wells, which were located either on a flat plate or a raised tube with varying well depths. This setup was designed to require coordinated finger movements during the task. Immediately after the DCL, the animals exhibited measurable behavioral deficits. These were characterized by significant increases in grasping speed squared and trial completion time, markedly widened movement trajectories of individual fingers, and abnormalities in inter-finger distance and orientation. Increased task difficulty was associated with more pronounced behavioral deficits. By three months post-DCL, video-based measurements indicated no significant recovery, even though global end-point performance had returned to baseline levels. Our findings demonstrate that deprivation of tactile information results in impaired dexterous hand behavior involving coordinated finger movements, and the impairment is sustained for 20 weeks. This spinal cord injury (SCI) model, along with DeepLapCut analysis, provides a valuable platform for separately evaluating sensory and motor functions and their contributions to dexterous hand behavior and may be used for evaluating therapeutic interventions using more sensitive behavioral outcome readouts.

5.
Magn Reson Imaging ; 113: 110221, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39173962

RESUMEN

Alterations in white matter (WM) microstructure of the central nervous system have been shown to be pathophysiological presentations of various neurodegenerative disorders. Current methods for measuring such WM features require ex vivo tissue samples analyzed using electron microscopy. Magnetic Resonance Imaging (MRI) diffusion-weighted pulse sequences provide a non-invasive tool for estimating such microstructural features in vivo. The current project investigated the use of two methods of analysis, including the ROI-based (Region of Interest, RBA) and voxel-based analysis (VBA), as well as four mathematical models of WM microstructure, including the ActiveAx Frequency-Independent Extra-Axonal Diffusion (AAI), ActiveAx Frequency-Dependent Extra-Axonal Diffusion (AAD), AxCaliber Frequency-Independent Extra-Axonal Diffusion (ACI), and AxCaliber Frequency-Dependent Extra-Axonal Diffusion (ACD) models. Two mice samples imaged at 7 T and 15.2 T were analyzed. Both the AAI and AAD models provide a single value for each of the fit parameters, including mean effective axon diameter AxD¯, packing fraction fin, intra-cellular and Din and extra-cellular Dex diffusion coefficients, as well as the frequency dependence of Dex, ßex for the AAD model. The ACI and ACD models provide this, in addition to a distribution of axon diameters for a chosen ROI. VBA extends this, providing a parameter value for each voxel within the selected ROI, at the cost of increased computational load and analysis time. Overall, RBA-ACD and VBA-AAD were found to be optimal for parameter fitting to physically relevant values in a reasonable time frame. A full comparison of each combination of RBA and VBA with AAI, AAD, ACI, and ACD is provided to give the reader sufficient information to make an informed decision of which model is best for their own experiments.


Asunto(s)
Sustancia Blanca , Sustancia Blanca/diagnóstico por imagen , Animales , Ratones , Imagen de Difusión por Resonancia Magnética/métodos , Axones/patología , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo/diagnóstico por imagen , Simulación por Computador , Reproducibilidad de los Resultados , Modelos Neurológicos , Interpretación de Imagen Asistida por Computador/métodos
6.
Magn Reson Med ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164611

RESUMEN

PURPOSE: This study aims to assess how T2 heterogeneity biases IMPULSED-derived metrics of tissue microstructure in solid tumors and evaluate the potential of estimating multi-compartmental T2 and microstructural parameters simultaneously. METHODS: This study quantifies the impact of T2 relaxation on IMPULSED-derived microstructural parameters using computer simulations and in vivo multi-TE IMPULSED MRI in five tumor models, including brain, breast, prostate, melanoma, and colon cancer. A comprehensive T2 + IMPULSED method was developed to fit multi-compartmental T2 and microstructural parameters simultaneously. A Bayesian model selection approach was carried out voxel-wisely to determine if the T2 heterogeneity needs to be included in IMPULSED MRI in cancer. RESULTS: Simulations suggest that T2 heterogeneity has a minor effect on the estimation of d in tissues with intermediate or high cell density, but significantly biases the estimation of v in $$ {v}_{in} $$ with low cell density. For the in vivo animal experiments, all IMPULSED metrics except v in $$ {v}_{in} $$ are statistically independent on TE. For B16 tumors, the IMPULSED-derived v in $$ {v}_{in} $$ exhibited a notable increase with longer TEs. For MDA-MB-231 tumors, IMPULSED-derived v in $$ {v}_{in} $$ showed a significant increase with increasing TEs. The T2 + IMPULSED-derived T 2 in $$ {T}_2^{in} $$ of all five tumor models are consistently smaller than T 2 ex $$ {T}_2^{ex} $$ . CONCLUSIONS: The findings from this study highlight two key observations: (i) TE has a negligible impact on IMPULSED-derived cell sizes, and (ii) the TE-dependence of IMPULSED-derived intracellular volume fractions used in T2 + IMPULSED modeling to estimate T 2 in $$ {T}_2^{in} $$ and T 2 ex $$ {T}_2^{ex} $$ . These insights contribute to the ongoing development and refinement of non-invasive MRI techniques for measuring cell sizes.

7.
Sci Rep ; 14(1): 16086, 2024 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-38992064

RESUMEN

The classical amyloid cascade hypothesis postulates that the aggregation of amyloid plaques and the accumulation of intracellular hyperphosphorylated Tau tangles, together, lead to profound neuronal death. However, emerging research has demonstrated that soluble amyloid-ß oligomers (SAßOs) accumulate early, prior to amyloid plaque formation. SAßOs induce memory impairment and disrupt cognitive function independent of amyloid-ß plaques, and even in the absence of plaque formation. This work describes the development and characterization of a novel anti-SAßO (E3) nanobody generated from an alpaca immunized with SAßO. In-vitro assays and in-vivo studies using 5XFAD mice indicate that the fluorescein (FAM)-labeled E3 nanobody recognizes both SAßOs and amyloid-ß plaques. The E3 nanobody traverses across the blood-brain barrier and binds to amyloid species in the brain of 5XFAD mice. Imaging of mouse brains reveals that SAßO and amyloid-ß plaques are not only different in size, shape, and morphology, but also have a distinct spatial distribution in the brain. SAßOs are associated with neurons, while amyloid plaques reside in the extracellular matrix. The results of this study demonstrate that the SAßO nanobody can serve as a diagnostic agent with potential theragnostic applications in Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Placa Amiloide , Anticuerpos de Dominio Único , Animales , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/inmunología , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/química , Ratones , Placa Amiloide/metabolismo , Enfermedad de Alzheimer/metabolismo , Humanos , Encéfalo/metabolismo , Encéfalo/patología , Barrera Hematoencefálica/metabolismo , Ratones Transgénicos , Camélidos del Nuevo Mundo , Modelos Animales de Enfermedad
8.
Proc Natl Acad Sci U S A ; 121(22): e2316117121, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38776372

RESUMEN

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.


Asunto(s)
Imagen por Resonancia Magnética , Saimiri , Médula Espinal , Sustancia Blanca , Animales , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiología , Médula Espinal/fisiología , Médula Espinal/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Descanso/fisiología , Oxígeno/sangre , Oxígeno/metabolismo , Masculino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/fisiología , Femenino
9.
Res Sq ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38559050

RESUMEN

The classical amyloid cascade hypothesis postulates that the aggregation of amyloid plaques and the accumulation of intracellular hyperphosphorylated Tau tangles, together, lead to profound neuronal death. However, emerging research has demonstrated that soluble amyloid-ß oligomers (SAßOs) accumulate early, prior to amyloid plaque formation. SAßOs induce memory impairment and disrupt cognitive function independent of amyloid-ß plaques, and even in the absence of plaque formation. This work describes the development and characterization of a novel anti-SAßO (E3) nanobody generated from an alpaca immunized with SAßO. In-vitro assays and in-vivo studies using 5XFAD mice indicate that the fluorescein (FAM)-labeled E3 nanobody recognizes both SAßOs and amyloid-ß plaques. The E3 nanobody traverses across the blood-brain barrier and binds to amyloid species in the brain of 5XFAD mice. Imaging of mouse brains reveals that SAßO and amyloid-ß plaques are not only different in size, shape, and morphology, but also have a distinct spatial distribution in the brain. SAßOs are associated with neurons, while amyloid plaques reside in the extracellular matrix. The results of this study demonstrate that the SAßO nanobody can serve as a diagnostic agent with potential theragnostic applications in Alzheimer's disease.

10.
Cereb Cortex ; 34(3)2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38517178

RESUMEN

Cognitive decline with aging involves multifactorial processes, including changes in brain structure and function. This study focuses on the role of white matter functional characteristics, as reflected in blood oxygenation level-dependent signals, in age-related cognitive deterioration. Building on previous research confirming the reproducibility and age-dependence of blood oxygenation level-dependent signals acquired via functional magnetic resonance imaging, we here employ mediation analysis to test if aging affects cognition through white matter blood oxygenation level-dependent signal changes, impacting various cognitive domains and specific white matter regions. We used independent component analysis of resting-state blood oxygenation level-dependent signals to segment white matter into coherent hubs, offering a data-driven view of white matter's functional architecture. Through correlation analysis, we constructed a graph network and derived metrics to quantitatively assess regional functional properties based on resting-state blood oxygenation level-dependent fluctuations. Our analysis identified significant mediators in the age-cognition relationship, indicating that aging differentially influences cognitive functions by altering the functional characteristics of distinct white matter regions. These findings enhance our understanding of the neurobiological basis of cognitive aging, highlighting the critical role of white matter in maintaining cognitive integrity and proposing new approaches to assess interventions targeting cognitive decline in older populations.


Asunto(s)
Disfunción Cognitiva , Sustancia Blanca , Humanos , Anciano , Sustancia Blanca/diagnóstico por imagen , Reproducibilidad de los Resultados , Mapeo Encefálico , Envejecimiento , Encéfalo/diagnóstico por imagen , Cognición , Imagen por Resonancia Magnética , Disfunción Cognitiva/diagnóstico por imagen
11.
Magn Reson Imaging ; 108: 11-21, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38309376

RESUMEN

Diffusion MRI of the spinal cord (SC) is susceptible to geometric distortion caused by field inhomogeneities, and prone to misalignment across time series and signal dropout caused by biological motion. Several modifications of image acquisition and image processing techniques have been introduced to overcome these artifacts, but their specific benefits are largely unproven and warrant further investigations. We aim to evaluate two specific aspects of image acquisition and processing that address image quality in diffusion studies of the spinal cord: susceptibility corrections to reduce geometric distortions, and cardiac triggering to minimize motion artifacts. First, we evaluate 4 distortion preprocessing strategies on 7 datasets of the cervical and lumbar SC and find that while distortion correction techniques increase geometric similarity to structural images, they are largely driven by the high-contrast cerebrospinal fluid, and do not consistently improve the geometry within the cord nor improve white-to-gray matter contrast. We recommend at a minimum to perform bulk-motion correction in preprocessing and posit that improvements/adaptations are needed for spinal cord distortion preprocessing algorithms, which are currently optimized and designed for brain imaging. Second, we design experiments to evaluate the impact of removing cardiac triggering. We show that when triggering is foregone, images are qualitatively similar to triggered sequences, do not have increased prevalence of artifacts, and result in similar diffusion tensor indices with similar reproducibility to triggered acquisitions. When triggering is removed, much shorter acquisitions are possible, which are also qualitatively and quantitatively similar to triggered sequences. We suggest that removing cardiac triggering for cervical SC diffusion can be a reasonable option to save time with minimal sacrifice to image quality.


Asunto(s)
Imagen de Difusión por Resonancia Magnética , Procesamiento de Imagen Asistido por Computador , Reproducibilidad de los Resultados , Procesamiento de Imagen Asistido por Computador/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Médula Espinal/diagnóstico por imagen , Encéfalo , Algoritmos , Artefactos , Imagen Eco-Planar/métodos
12.
bioRxiv ; 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38328148

RESUMEN

White matter signals in resting state blood oxygen level dependent functional magnetic resonance (BOLD-fMRI) have been largely discounted, yet there is growing evidence that these signals are indicative of brain activity. Understanding how these white matter signals capture function can provide insight into brain physiology. Moreover, functional signals could potentially be used as early markers for neurological changes, such as in Alzheimer's Disease. To investigate white matter brain networks, we leveraged the OASIS-3 dataset to extract white matter signals from resting state BOLD-FMRI data on 711 subjects. The imaging was longitudinal with a total of 2,026 images. Hierarchical clustering was performed to investigate clusters of voxel-level correlations on the timeseries data. The stability of clusters was measured with the average Dice coefficients on two different cross fold validations. The first validated the stability between scans, and the second validated the stability between subject populations. Functional clusters at hierarchical levels 4, 9, 13, 18, and 24 had local maximum stability, suggesting better clustered white matter. In comparison with JHU-DTI-SS Type-I Atlas defined regions, clusters at lower hierarchical levels identified well defined anatomical lobes. At higher hierarchical levels, functional clusters mapped motor and memory functional regions, identifying 50.00%, 20.00%, 27.27%, and 35.14% of the frontal, occipital, parietal, and temporal lobe regions respectively.

13.
Cancer Med ; 13(3): e6812, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38239047

RESUMEN

BACKGROUND: It has been shown that tumor microenvironment (TME) hydroxyapatite (HAP) is typically associated with many malignancies and plays a role in tumor progression and growth. Additionally, acidosis in the TME has been reported to play a key role in selecting for a more aggressive tumor phenotype, drug resistance and desensitization to immunotherapy for many types of cancers. TME-HAP is an attractive target for tumor detection and treatment development since HAP is generally absent from normal soft tissue. We provide strong evidence that dissolution of hydroxyapatite (HAP) within the tumor microenvironment (TME-HAP) using a novel therapeutic can be used to kill cancer cells both in vitro and in vivo with minimal adverse effects. METHODS: We developed an injectable cation exchange nano particulate sulfonated polystyrene solution (NSPS) that we engineered to dissolve TME-HAP, inducing localized acute alkalosis and inhibition of tumor growth and glucose metabolism. This was evaluated in cell culture using 4T1, MDA-MB-231 triple negative breast cancer cells, MCF10 normal breast cells, and H292 lung cancer cells, and in vivo using orthotopic mouse models of cancer that contained detectable microenvironment HAP including breast (MMTV-Neu, 4T1, and MDA-MB-231), prostate (PC3) and colon (HCA7) cancer using 18 F-NaF for HAP and 18 F-FDG for glucose metabolism with PET imaging. On the other hand, H292 lung tumor cells that lacked detectable microenvironment HAP and MCF10a normal breast cells that do not produce HAP served as negative controls. Tumor microenvironment pH levels following injection of NSPS were evaluated via Chemical Exchange Saturation (CEST) MRI and via ex vivo methods. RESULTS: Within 24 h of adding the small concentration of 1X of NSPS (~7 µM), we observed significant tumor cell death (~ 10%, p < 0.05) in 4T1 and MDA-MB-231 cell cultures that contain HAP but ⟨2% in H292 and MCF10a cells that lack detectable HAP and in controls. Using CEST MRI, we found extracellular pH (pHe) in the 4T1 breast tumors, located in the mammary fat pad, to increase by nearly 10% from baseline before gradually receding back to baseline during the first hour post NSPS administration. in the tumors that contained TME-HAP in mouse models, MMTV-Neu, 4T1, and MDA-MB-231, PC3, and HCA7, there was a significant reduction (p<0.05) in 18 F-Na Fuptake post NSPS treatment as expected; 18 F- uptake in the tumor = 3.8 ± 0.5 %ID/g (percent of the injected dose per gram) at baseline compared to 1.8 ±0.5 %ID/g following one-time treatment with 100 mg/kg NSPS. Of similar importance, is that 18 F-FDG uptake in the tumors was reduced by more than 75% compared to baseline within 24 h of treatment with one-time NSPS which persisted for at least one week. Additionally, tumor growth was significantly slower (p < 0.05) in the mice treated with one-time NSPS. Toxicity showed no evidence of any adverse effects, a finding attributed to the absence of HAP in normal soft tissue and to our therapeutic NSPS having limited penetration to access HAP within skeletal bone. CONCLUSION: Dissolution of TME-HAP using our novel NSPS has the potential to provide a new treatment paradigm to enhance the management of cancer patients with poor prognosis.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias Pulmonares , Humanos , Masculino , Animales , Ratones , Preparaciones Farmacéuticas , Fluorodesoxiglucosa F18 , Inmunoterapia , Alcanosulfonatos , Glucosa , Hidroxiapatitas , Microambiente Tumoral
14.
bioRxiv ; 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38260265

RESUMEN

Understanding the intricate interplay between gray matter (GM) and white matter (WM) is crucial for deciphering the complex activities of the brain. While diffusion tensor imaging (DTI) has advanced the mapping of these structural pathways, the relationship between structural connectivity (SC) and functional connectivity (FC) remains inadequately understood. This study addresses the need for a more integrative approach by mapping the importance of the inter-GM functional link to its structural counterparts in WM. This mapping yields a spatial distribution of engagement that is not only highly reproducible but also aligns with direct structural, functional, and bioenergetic measures within WM, illustrating a notable interdependence between the function of GM and the characteristics of WM. Additionally, our research has uncovered a set of unique engagement modes through a clustering analysis of window-wise engagement maps, highlighting the dyanmic nature of the engagement. The engagement along with their temporal variations revealed significant differences across genders and age groups. These findings suggest the potential of WM engagement as a biomarker for neurological and cognitive conditions, offering a more nuanced understanding of individualized brain activity and connectivity patterns.

15.
Sci Adv ; 10(4): eadi0616, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38277462

RESUMEN

Correlations between magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) signals from pairs of gray matter areas are used to infer their functional connectivity, but they are unable to describe how white matter is engaged in brain networks. Recently, evidence that BOLD signals in white matter are robustly detectable and are modulated by neural activities has accumulated. We introduce a three-way correlation between BOLD signals from pairs of gray matter volumes (nodes) and white matter bundles (edges) to define the communication connectivity through each white matter bundle. Using MRI images from publicly available databases, we show, for example, that the three-way connectivity is influenced by age. By integrating functional MRI signals from white matter as a third component in network analyses, more comprehensive descriptions of brain function may be obtained.


Asunto(s)
Sustancia Blanca , Sustancia Blanca/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Imagen por Resonancia Magnética , Mapeo Encefálico/métodos
16.
Behav Brain Res ; 459: 114808, 2024 02 29.
Artículo en Inglés | MEDLINE | ID: mdl-38081518

RESUMEN

A mathematical model-based parcellation of magnetic resonance diffusion tensor images (DTI) has been developed to quantify progressive changes in three types of tissues - grey (GM), white matter (WM), and damaged spinal cord tissue, along with behavioral assessments over a 6 month period following targeted spinal cord injuries (SCI) in monkeys. Sigmoid Gompertz function based fittings of DTI metrics provide early indicators that correlate with, and predict, recovery of hand grasping behavior. Our three tissue pool model provided unbiased, data-driven segmentation of spinal cord images and identified DTI metrics that can serve as reliable biomarkers of severity of spinal cord injuries and predictors of behavioral outcomes.


Asunto(s)
Imagen de Difusión Tensora , Traumatismos de la Médula Espinal , Animales , Humanos , Saimiri , Imagen de Difusión Tensora/métodos , Médula Espinal/diagnóstico por imagen , Médula Espinal/patología , Imagen de Difusión por Resonancia Magnética , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/patología
17.
J Magn Reson Imaging ; 59(2): 575-584, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37218596

RESUMEN

BACKGROUND: Breast cancer treatment response evaluation using the response evaluation criteria in solid tumors (RECIST) guidelines, based on tumor volume changes, has limitations, prompting interest in novel imaging markers for accurate therapeutic effect determination. PURPOSE: To use MRI-measured cell size as a new imaging biomarker for assessing chemotherapy response in breast cancer. STUDY TYPE: Longitudinal; animal model. STUDY POPULATION: Triple-negative human breast cancer cell (MDA-MB-231) pellets (4 groups, n = 7) treated with dimethyl sulfoxide (DMSO) or 10 nM of paclitaxel for 24, 48, and 96 hours, and 29 mice with MDA-MB-231 tumors in right hind limbs treated with paclitaxel (n = 16) or DMSO (n = 13) twice weekly for 3 weeks. FIELD STRENGTH/SEQUENCE: Oscillating gradient spin echo and pulsed gradient spin echo sequences at 4.7 T. ASSESSMENT: MDA-MB-231 cells were analyzed using flowcytometry and light microscopy to assess cell cycle phases and cell size distribution. MDA-MB-231 cell pellets were MR imaged. Mice were imaged weekly, with 9, 6, and 14 being sacrificed for histology after MRI at weeks 1, 2, and 3, respectively. Microstructural parameters of tumors/cell pellets were derived by fitting diffusion MRI data to a biophysical model. STATISTICAL TESTS: One-way ANOVA compared cell sizes and MR-derived parameters between treated and control samples. Repeated measures 2-way ANOVA with Bonferroni post-tests compared temporal changes in MR-derived parameters. A P-value <0.05 was considered statistically significant. RESULTS: In vitro experiments showed that the mean MR-derived cell sizes of paclitaxel-treated cells increased significantly with a 24-hours treatment and decreased (P = 0.06) with a 96-hour treatment. For in vivo xenograft experiments, the paclitaxel-treated tumors showed significant decreases in cell size at later weeks. MRI observations were supported by flowcytometry, light microscopy, and histology. DATA CONCLUSIONS: MR-derived cell size may characterize the cell shrinkage during treatment-induced apoptosis, and may potentially provide new insights into the assessment of therapeutic response. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 4.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Femenino , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Dimetilsulfóxido/uso terapéutico , Línea Celular Tumoral , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Imagen por Resonancia Magnética/métodos , Tamaño de la Célula
18.
Mol Imaging Biol ; 26(2): 240-252, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38151582

RESUMEN

PURPOSE: The degree and dynamic progression of neuroinflammation after traumatic spinal cord injuries (SCI) are crucial determinants of the severity of injury and potential for recovery. We used Positron Emission Tomography (PET) to monitor neuroinflammation longitudinally, correlating it with Chemical Exchange Saturation Transfer (CEST) Magnetic Resonance Imaging (MRI) and behavior in contusion-injured rats. These studies help validate CEST metrics and confirm how imaging may be used to evaluate the efficacy of therapies and understand their mechanisms of action. PROCEDURES: 12 SCI and 4 sham surgery rats were subjected to CEST MRI and PET-Translocator Protein (TSPO) scans for 8 weeks following injury. Z-spectra from the SCI were analyzed using a 5-Lorentzian pool model for fitting. Weekly motor and somatosensory behavior were correlated with imaging metrics, which were validated through post-mortem histological and immuo-staining using ionized calcium-binding adaptor protein-1 (iba-1, microglia) and glial fibrillary acidic protein (GFAP, astrocytes). RESULTS: PET-TSPO showed widespread inflammation and post-mortem histology confirmed the presence of activated microglia. Changes in CEST and nuclear Overhauser Effect (NOE) peaks at 3.5 ppm and -1.6 ppm respectively were largest within the first week after injury and more pronounced in rostral versus caudal segments. These temporal indices of neuroinflammation corresponded to the recovery of locomotor behaviors and somatic sensation in rats with moderate contusion injury. The results confirm that CEST MRI metrics are sensitive indices of states of neuroinflammation within injured spinal cords. CONCLUSIONS: The detection of dynamic spatiotemporal features of neuroinflammation progression underscores the importance of considering their timings and locations for neuroprotective and anti-inflammatory therapies. The availability of noninvasive MRI indices of neuroinflammation may facilitate clinical trials aimed at treatments that promote recovery after SCI.


Asunto(s)
Contusiones , Traumatismos de la Médula Espinal , Ratas , Animales , Enfermedades Neuroinflamatorias , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Médula Espinal/patología , Inflamación/metabolismo , Proteínas Portadoras/metabolismo
19.
J Control Release ; 363: 707-720, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37827222

RESUMEN

The use of focused ultrasound to open the blood-brain barrier (BBB) has the potential to deliver drugs to specific regions of the brain. The size of the BBB opening and ability to localize the opening determines the spatial extent and is a limiting factor in many applications of BBB opening where targeting a small brain region is desired. Here we evaluate the performance of a system designed for small opening volumes and highlight the unique challenges associated with pushing the spatial precision of this technique. To achieve small volume openings in cortical regions of the macaque brain, we tested a custom 1 MHz array transducer integrated into a magnetic resonance image-guided focused ultrasound system. Using real-time cavitation monitoring, we demonstrated twelve instances of single sonication, small volume BBB opening with average volumes of 59 ± 37 mm3 and 184 ± 2 mm3 in cortical and subcortical targets, respectively. We found high correlation between subject-specific acoustic simulations and observed openings when incorporating grey matter segmentation (R2 = 0.8577), and the threshold for BBB opening based on simulations was 0.53 MPa. Analysis of MRI-based safety assessment and cavitation signals indicate a safe pressure range for 1 MHz BBB opening and suggest that our system can be used to deliver drugs and gene therapy to small brain regions.


Asunto(s)
Barrera Hematoencefálica , Macaca , Animales , Barrera Hematoencefálica/patología , Encéfalo/diagnóstico por imagen , Ultrasonografía , Sonicación/métodos , Imagen por Resonancia Magnética , Microburbujas
20.
bioRxiv ; 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37808645

RESUMEN

Characterizing how, when and where the human brain changes across the lifespan is fundamental to our understanding of developmental processes of childhood and adolescence, degenerative processes of aging, and divergence from normal patterns in disease and disorders. We aimed to provide detailed descriptions of white matter pathways across the lifespan by thoroughly characterizing white matter microstructure, white matter macrostructure, and morphology of the cortex associated with white matter pathways. We analyzed 4 large, high-quality, publicly-available datasets comprising 2789 total imaging sessions, and participants ranging from 0 to 100 years old, using advanced tractography and diffusion modeling. We first find that all microstructural, macrostructural, and cortical features of white matter bundles show unique lifespan trajectories, with rates and timing of development and degradation that vary across pathways - describing differences between types of pathways and locations in the brain, and developmental milestones of maturation of each feature. Second, we show cross-sectional relationships between different features that may help elucidate biological changes occurring during different stages of the lifespan. Third, we show unique trajectories of age-associations across features. Finally, we find that age associations during development are strongly related to those during aging. Overall, this study reports normative data for several features of white matter pathways of the human brain that will be useful for studying normal and abnormal white matter development and degeneration.

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