Correction for fast pseudo-diffusive fluid motion contaminations in diffusion tensor imaging

In this prospective study, we quantified the fast pseudo-diffusion contamination by blood perfusion or cerebrospinal fluid (CSF) intravoxel incoherent movements on the measurement of the diffusion tensor metrics in healthy brain tissue. Diffusion-weighted imaging (TR/TE = 4100 ms/90 ms; b-values: 0, 5, 10, 20, 35, 55, 80, 110, 150, 200, 300, 500, 750, 1000, 1300 s/mm2, 20 diffusion-encoding directions) was performed on a cohort of five healthy volunteers at 3 Tesla. The projections of the diffusion tensor along each diffusion-encoding direction were computed using a two b-value approach (2b), by fitting the signal to a monoexponential curve (mono), and by correcting for fast pseudo-diffusion compartments using the biexponential intravoxel incoherent motion model (IVIM) (bi). Fractional Anisotropy (FA) and Mean Diffusivity (MD) of the diffusion tensor were quantified in regions of interest drawn over white matter areas, gray matter areas, and the ventricles. A significant dependence of the MD from the evaluation method was found in all selected regions. A lower MD was computed when accounting for the fast-diffusion compartments. A larger dependence was found in the nucleus caudatus (bi: median 0.86 10-3 mm2/s, Δ2b: -11.2%, Δmono: -14.4%; p = 0.007), in the anterior horn (bi: median 2.04 10-3 mm2/s, Δ2b: -9.4%, Δmono: -11.5%, p = 0.007) and in the posterior horn of the lateral ventricles (bi: median 2.47 10-3 mm2/s, Δ2b: -5.5%, Δmono: -11.7%; p = 0.007). Also for the FA, the signal modeling affected the computation of the anisotropy metrics. The deviation depended on the evaluated region with significant differences mainly in the nucleus caudatus (bi: median 0.15, Δ2b: +39.3%, Δmono: +14.7%; p = 0.022) and putamen (bi: median 0.19, Δ2b: +3.1%, Δmono: +17.3%; p = 0.015). Fast pseudo-diffusive regimes locally affect diffusion tensor imaging (DTI) metrics in the brain. Here, we propose the use of an IVIM-based method for correction of signal contaminations through CSF or perfusion

Signal to Noise and b-value Analysis for Optimal Intra-Voxel Incoherent Motion Imaging in the Brain

Intravoxel incoherent motion (IVIM) is a method that can provide quantitative information about perfusion in the human body, in vivo, and without contrast agent. Unfortunately, the IVIM perfusion parameter maps are known to be relatively noisy in the brain, in particular for the pseudo-diffusion coefficient, which might hinder its potential broader use in clinical applications. Therefore, we studied the conditions to produce optimal IVIM perfusion images in the brain. IVIM imaging was performed on a 3-Tesla clinical system in four healthy volunteers, with 16 b values 0, 10, 20, 40, 80, 110, 140, 170, 200, 300, 400, 500, 600, 700, 800, 900 s/mm2, repeated 20 times. We analyzed the noise characteristics of the trace images as a function of b-value, and the homogeneity of the IVIM parameter maps across number of averages and sub-sets of the acquired b values. We found two peaks of noise of the trace images as function of b value, one due to thermal noise at high b-value, and one due to physiological noise at low b-value. The selection of b value distribution was found to have higher impact on the homogeneity of the IVIM parameter maps than the number of averages. Based on evaluations, we suggest an optimal b value acquisition scheme for a 12 min scan as 0 (7), 20 (4), 140 (19), 300 (9), 500 (19), 700 (1), 800 (4), 900 (1) s/mm2.Comment: 26 pages, 5 Figure

Current Understanding of the Anatomy, Physiology, and Magnetic Resonance Imaging of Neurofluids: Update From the 2022 "ISMRM Imaging Neurofluids Study group" Workshop in Rome

Neurofluids is a term introduced to define all fluids in the brain and spine such as blood, cerebrospinal fluid, and interstitial fluid. Neuroscientists in the past millennium have steadily identified the several different fluid environments in the brain and spine that interact in a synchronized harmonious manner to assure a healthy microenvironment required for optimal neuroglial function. Neuroanatomists and biochemists have provided an incredible wealth of evidence revealing the anatomy of perivascular spaces, meninges and glia and their role in drainage of neuronal waste products. Human studies have been limited due to the restricted availability of noninvasive imaging modalities that can provide a high spatiotemporal depiction of the brain neurofluids. Therefore, animal studies have been key in advancing our knowledge of the temporal and spatial dynamics of fluids, for example, by injecting tracers with different molecular weights. Such studies have sparked interest to identify possible disruptions to neurofluids dynamics in human diseases such as small vessel disease, cerebral amyloid angiopathy, and dementia. However, key differences between rodent and human physiology should be considered when extrapolating these findings to understand the human brain. An increasing armamentarium of noninvasive MRI techniques is being built to identify markers of altered drainage pathways. During the three-day workshop organized by the International Society of Magnetic Resonance in Medicine that was held in Rome in September 2022, several of these concepts were discussed by a distinguished international faculty to lay the basis of what is known and where we still lack evidence. We envision that in the next decade, MRI will allow imaging of the physiology of neurofluid dynamics and drainage pathways in the human brain to identify true pathological processes underlying disease and to discover new avenues for early diagnoses and treatments including drug delivery. Evidence level: 1. Technical Efficacy: Stage 3

Vascular Stiffening and the Brain: Direct Measures of Cerebrovascular Stiffness in Aging and Vasodilation

Dampening of pulsatile pressure waves within blood vessels is an essential feature of the arterial system. Vascular stiffening increases the speed and the pulsatile energy of the pressure wave, leaving low resistance organs like the brain vulnerable to microvascular mechanical damage. Due to access limitations, the effect of cerebrovascular stiffening on brain structure and neurological outcomes remains unknown. The purpose of this thesis was to assess the influence of vascular stiffening in peripheral arteries on white matter integrity (WMLv) (Chapter 2), obtain direct measures of cerebrovascular stiffness via phase contrast magnetic resonance imaging (PCMRI) (Chapter 3), and examine the impact of acute vasodilation on cerebrovascular stiffness (Chapter 4). We found that ischemic heart disease patients (IHD) had greater vascular stiffness compared with controls. However, IHD status did not influence WMLv. Regardless of vascular pathology, common carotid stiffness and ultrasound-based carotid-cerebral pulse wave transit times were associated with WMLv independently. Therefore, we applied PCMRI to the cerebral vessels to acquire direct measures of cerebrovascular stiffness in the internal carotid (ICA) and middle cerebral (MCA) arteries. Using cardiac-gated PCRMI, we collected blood flow velocity data at multiple segments of the ICA (icaPWV) and M1-M2 segment of the MCA (mcaPWV) to construct time–intensity curves and calculate PWV at temporal resolutions up to 25ms. We demonstrated that mcaPWV can detect vascular stiffening in a cross-section of young and older healthy individuals. Additionally, PWV increases from extracranial to intracranial segments, and this acceleration is amplified with age. We then measured peripheral and intracranial vascular stiffness in response to vasodilation using hypercapnia (HC; 6% CO2, 21% O2, balanced N2) and nitroglycerin (NTG; 0.4mg, sublingual) in healthy young adults. Vasodilation in the MCA increased PWV and characteristic impedance. Additionally, the preferential effect of HC on conduit and downstream vascular properties of cerebral vessels versus non-specific conduit vasodilation of NTG suggests that multiple mechanisms may contribute to cerebrovascular stiffening. This thesis provides a method to obtain direct measures of intracranial PWV and demonstrates the capacity for acute modification of cerebrovasculature stiffness. This work may advance future understanding of cerebrovascular changes, damage, and therapeutics in vulnerable populations

Developing novel non-invasive MRI techniques to assess cerebrospinal fluid-interstitial fluid (CSF-ISF) exchange

The pathological cascade of events in Alzheimer’s disease (AD) is initiated decades prior to the onset of symptoms. Despite intensive research, the relative time-course/interaction of these events is yet to be determined. Recent evidence suggests that impairments to brain clearance (facilitated by the compartmental exchange of cerebrospinal-fluid (CSF) with interstitial-fluid (ISF)), contributes to the build-up of amyloid and tau (AD hallmarks). Therefore, abnormalities in CSF-ISF exchange dynamics, may represent an early driver of downstream events. Clinical evaluation of this hypothesis is hampered due to the lack of non-invasive CSF-ISF exchange assessment techniques. In this thesis, the primary aim was to develop a physiologically relevant, non-invasive CSF-ISF exchange assessment technique that would circumvent the limitations associated with current procedures (primarily their invasiveness). Towards this goal, animal studies were conducted to investigate the feasibility of a contrast enhanced-magnetic resonance imaging (CE-MRI) approach as a potential non-invasive CSF-ISF exchange imaging technique. Another aim of this thesis was to investigate whether the proposed MRI platform could detect abnormalities in CSF-ISF exchange, a condition hypothesised to occur in the early stages of AD. As such, pharmacological intervention studies were conducted to alter CSF-ISF exchange dynamics. CE-MRI, in conjunction with high-level image post-processing, demonstrated high sensitivity to physiological CSF-ISF exchange. This novel, non-invasive platform, captured dynamic, whole-brain infiltration of contrast agent from the blood to the CSF and into the parenchyma, via a pathway named ‘VEntricular-Cerebral TranspORt (VECTOR)’. Additionally, the platform detected significant abnormalities in CSF-ISF exchange following pharmacological intervention, demonstrating the potential of VECTOR in the study of the parenchymal accumulation of aberrant proteins. Development of this platform is a breakthrough step towards the clinical assessment of CSF-ISF exchange abnormalities to study its role in disease onset/progression, an approach that may inform understanding of the causal sequence of pathological events that occurs in AD development

MR Sequence Development for Imaging Venous Blood Flow in the Leg

Deep Vein Thrombosis is a common complication in bed-ridden patients, described as the main cause of preventable hospital deaths in the UK (NICE 2010). Mechanical prophylaxis aims to promote venous flow, either statically with compression stockings, or dynamically with intermittent pneumatic compression or electrical muscle stimulation. Previous studies used ultrasound for venous flow measurements, limited to a single deep vein at a time, and some anatomical MRI for investigating the mechanisms behind these prophylaxes. MRI velocity mapping is used clinically in the arterial system where gating enables data accumulation over multiple cardiac cycles. This thesis describes the development of two real-time MRI spiral velocity mapping sequences for imaging venous blood flow in the leg, where venous flow variability is largely unrelated to the cardiac cycle. Real-time imaging with spiral gradient readouts minimised image duration. A phase-image fitting technique requiring only a velocity-encoded phase image was implemented for acceleration. For in vivo comparison, conventional flow imaging required metronome-guided breathing for a regular venous flow waveform. The long spiral readouts were sensitive to off-resonance and flow artefacts, where some unpublished effects were investigated. The off-resonance associated with deoxygenation of venous blood did not cause notable spiral artefacts, but disrupted the phase-image fitting technique and required correction with a pre-scan. The spiral flow methods demonstrated increased venous blood velocity and flow during application of mechanical compression. Metronome-guided breathing was also applied to vein wall imaging, where it detected wall thickening in patients with Behçet’s disease compared with normal subjects. For the first time, this thesis evaluated real-time MRI spiral velocity mapping of venous blood velocity and flow. The high resolution (1mm) and short image time required caused challenging off-resonance and flow artefacts. With some limitations, real-time spiral flow MRI during operation of compression devices may assist in their optimisation

Exploring the developing preterm brain with diffusion tensor magnetic resonance imaging

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