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Biomedical subjects

Peter C M van Zijl

Publications and source records attributed to Peter C M van Zijl.

At least 19 recordsLinked to original sources

Detection of the ischemic penumbra using pH-weighted MRI.

The classic definition of the ischemic penumbra is a hypoperfused region in which metabolism is impaired, but still sufficient to maintain cellular polarization. Perfusion- and diffusion-weighted MRI (PWI, DWI) can identify regions of reduced perfusion and cellular depolarization, respectively, but it often remains unclear whether a PWI-DWI mismatch corresponds to benign oligemia or a true penumbra. We hypothesized that pH-weighted MRI (pHWI) can subdivide the PWI-DWI mismatch into these regions. Twenty-one rats underwent permanent middle cerebral artery occlusion and ischemic evolution over the first 3.5 h post-occlusion was studied using multiparametric MRI. End point was the stroke area defined by T(2)-hyperintensity at 24 h. In the acute phase, areas of reduced pH were always larger than or equal to DWI deficits and smaller than or equal to PWI deficits. Group analysis showed that pHWI deficits during this phase coincided with the resulting infarct area at endpoint. Final infarcts were smaller than PWI deficits (range 65% to 90%, depending on the severity of the occlusion) and much larger than acute DWI deficits. These data suggest that the outer boundary of the hypoperfused area showing a decrease in pH without DWI abnormality may correspond to the outer boundary of the ischemic penumbra, while the hypoperfused region at normal pH may correspond to benign oligemia. These first results show that pHWI can provide information complementary to PWI and DWI in the delineation of ischemic tissue.

Animals↗

White and gray matter development in human fetal, newborn and pediatric brains.

Brain anatomy is characterized by dramatic growth from the end of the second trimester through the neonatal stage. The characterization of normal axonal growth of the white matter tracts has not been well-documented to date and could provide important clues to understanding the extensive inhomogeneity of white matter injuries in cerebral palsy (CP) patients. However, anatomical studies of human brain development during this period are surprisingly scarce and histology-based atlases have become available only recently. Diffusion tensor magnetic resonance imaging (DTMRI) can reveal detailed anatomy of white matter. We acquired diffusion tensor images (DTI) of postmortem fetal brain samples and in vivo neonates and children. Neural structures were annotated in two-dimensional (2D) slices, segmented, measured, and reconstructed three-dimensionally (3D). The growth status of various white matter tracts was evaluated on cross-sections at 19-20 gestational weeks, and compared with 0-month-old neonates and 5- to 6-year-old children. Limbic, commissural, association, and projection white matter tracts and gray matter structures were illustrated in 3D and quantitatively characterized to assess their dynamic changes. The overall pattern of the time courses for the development of different white matter is that limbic fibers develop first and association fibers last and commissural and projection fibers are forming from anterior to posterior part of the brain. The resultant DTMRI-based 3D human brain data will be a valuable resource for human brain developmental study and will provide reference standards for diagnostic radiology of premature newborns.

Adult↗

DtiStudio: resource program for diffusion tensor computation and fiber bundle tracking.

A versatile resource program was developed for diffusion tensor image (DTI) computation and fiber tracking. The software can read data formats from a variety of MR scanners. Tensor calculation is performed by solving an over-determined linear equation system using least square fitting. Various types of map data, such as tensor elements, eigenvalues, eigenvectors, diffusion anisotropy, diffusion constants, and color-coded orientations can be calculated. The results are visualized interactively in orthogonal views and in three-dimensional mode. Three-dimensional tract reconstruction is based on the Fiber Assignment by Continuous Tracking (FACT) algorithm and a brute-force reconstruction approach. To improve the time and memory efficiency, a rapid algorithm to perform the FACT is adopted. An index matrix for the fiber data is introduced to facilitate various types of fiber bundles selection based on approaches employing multiple regions of interest (ROIs). The program is developed using C++ and OpenGL on a Windows platform.

Algorithms↗

Image contrast using the secondary and tertiary eigenvectors in diffusion tensor imaging.

Diffusion tensor imaging (DTI) is a new imaging modality that can provide unique information on brain white matter anatomy. Measurements of water diffusion constant along multiple axes are fitted to a tensor model, from which the diffusion anisotropy and dominant fiber orientation can be estimated. Even though the tensor model is an oversimplification of the underlying neuroanatomy, information within the tensor has not been fully utilized in routine research and clinical studies. In this study we proposed and examined the properties and anatomical contents of several DTI-derived image contrasts that utilize all three eigenvectors. The new contrasts are studied and validated using known anatomical structures in ex vivo mouse brain and embryonic mouse cortex. Application to human white matter is illustrated. Our results suggest that when these contrasts are combined with a priori anatomical knowledge, they reveal neuroanatomical information that is useful for tissue segmentation and diagnosis of white matter lesions.

Animals↗

Quantifying exchange rates in chemical exchange saturation transfer agents using the saturation time and saturation power dependencies of the magnetization transfer effect on the magnetic resonance imaging signal (QUEST and QUESP): Ph calibration for poly-L-lysine and a starburst dendrimer.

The ability to measure proton exchange rates in tissue using MRI would be very useful for quantitative assessment of magnetization transfer properties, both in conventional MT imaging and in the more recent chemical exchange saturation transfer (CEST) approach. CEST is a new MR contrast mechanism that depends on several factors, including the exchange rate of labile protons in the agent in a pH-dependent manner. Two new methods to monitor local exchange rate based on CEST are introduced. The two MRI-compatible approaches to measure exchange are quantifying exchange using saturation time (QUEST) dependence and quantifying exchange using saturation power (QUESP) dependence. These techniques were applied to poly-L-lysine (PLL) and a generation-5 polyamidoamine dendrimer (SPD-5) to measure the pH dependence of amide proton exchange rates in the physiologic range. Data were fit both to an analytical expression and to numerical solutions to the Bloch equations. Results were validated by comparison with exchange rates determined by two established spectroscopic methods. The exchange rates determined using the four methods were pooled for the pH-calibration curve of the agents consisting of contributions from spontaneous (k0) acid catalyzed (ka), and base catalyzed (kb) exchange rate constants. These constants were k0 = 68.9 Hz, ka = 1.21 Hz, kb = 1.92 x 10(9) Hz, and k0 = 106.4 Hz, ka = 25.8 Hz, kb = 5.45 x 10(8) Hz for PLL and SPD-5, respectively, showing the expected predominance of base-catalyzed exchange for these amide protons.

Calibration↗

Stem cell profiling by nuclear magnetic resonance spectroscopy.

The classification of embryonic and adult stem cells, including their derivatives, is still limited, and often these cells are best defined by their functional properties. Recent gene array studies have yielded contradictory results. Also, very little is known about the metabolic properties of these exciting cells. In this study, proton (1H) NMR spectroscopy was used to identify the major low-molecular-weight metabolites in murine embryonic stem cells (ESC) and their neural stem cell (NSC) derivatives. ESC are characterized by an unusually low number of NMR-detectable metabolites, high phosphocholine (PC) content, and nondetectable glycerophosphocholine (GPC). The metabolic profiles of NSC resemble glial cells and oligodendrocyte progenitors, but with considerably higher PC, GPC, and myo-inositol content. The results suggest that NMR spectroscopy in vitro can provide markers to study the effects of differentiation on cell metabolism, and potentially to assess stem cell preparations for differentiation status.

Animals↗

Detrimental effects of BOLD signal in arterial spin labeling fMRI at high field strength.

Arterial spin labeling (ASL) MRI is a useful technique for noninvasive measurement of cerebral blood flow (CBF) in humans. High field strength provides a unique advantage for ASL because of longer blood T(1) relaxation times, making this technique a promising quantitative approach for functional brain mapping. However, higher magnetic field also introduces new challenges. Here it is shown that the CBF response determined using ASL functional MRI (fMRI) at 3.0 T contains significant contamination from blood-oxygenation-level-dependent (BOLD) effects. Due to interleaved acquisitions of label and control images, difference in blood oxygenation status between these two scans can cause incomplete cancellation of the static signal upon image subtraction, resulting in a BOLD-related artifact in the estimated CBF hemodynamics. If not accounted for, such an effect can complicate the interpretation of the ASL results, e.g., causing a delayed onset and offset of the response, or inducing an artifactual poststimulus undershoot. The BOLD contribution also decreases the sensitivity of ASL-based fMRI. Correction methods are proposed to reduce the artifact, giving increased number of activated voxels (18+/-5%, P=0.006) and more accurate estimation of CBF temporal characteristics.

Algorithms↗

Amide proton transfer imaging of human brain tumors at 3T.

Amide proton transfer (APT) imaging is a technique in which the nuclear magnetization of water-exchangeable amide protons of endogenous mobile proteins and peptides in tissue is saturated, resulting in a signal intensity decrease of the free water. In this work, the first human APT data were acquired from 10 patients with brain tumors on a 3T whole-body clinical scanner and compared with T1- (T1w) and T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and diffusion images (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)). The APT-weighted images provided good contrast between tumor and edema. The effect of APT was enhanced by an approximate 4% change in the water signal intensity in tumor regions compared to edema and normal-appearing white matter (NAWM). These preliminary data from patients with brain tumors show that the APT is a unique contrast that can provide complementary information to standard clinical MRI measures.

Algorithms↗

Pulsed magnetization transfer imaging with body coil transmission at 3 Tesla: feasibility and application.

Pulsed magnetization transfer (MT) imaging has been applied to quantitatively assess brain pathology in several diseases, especially multiple sclerosis (MS). To date, however, because of the high power deposition associated with the use of short, rapidly repeating MT prepulses, clinical application has been limited to lower field strengths. The contrast-to-noise ratio (CNR) of MT is limited, and this method would greatly benefit from the use of higher magnetic fields and phased-array coil reception. However, power deposition is proportional to the square of the magnetic field and scales with coil size, and MT experiments are already close to the SAR limit at 1.5T even when smaller transmit coils are used instead of the body coil. Here we show that these seemingly great obstacles can be ameliorated by the increased T(1) of tissue water at higher field, which allows for longer maintenance of sufficiently high saturation levels while using a reduced duty cycle. This enables a fast (5-6 min) high-resolution (1.5 mm isotropic) whole-brain MT acquisition with excellent anatomical visualization of gray matter (GM) and white matter (WM) structures, and even substructures. The method is demonstrated in nine normal volunteers and five patients with relapsing remitting MS (RRMS), and the results show a clear delineation of heterogeneous lesions.

Adult↗

Theoretical and experimental investigation of the VASO contrast mechanism.

Vascular space occupancy (VASO)-dependent functional MRI (fMRI) is a blood-nulling technique capable of generating microvascular cerebral blood volume (CBV)-weighted images. It is shown that at high magnetic field (3.0T) and high spatial resolution (1.89 x 1.89 x 3 mm(3)), the VASO signal changes are too large (6-7%) to originate from CBV effects alone. Additional contributions are investigated theoretically and experimentally as a function of MRI parameters (TR and TE), as well as the signal-to-noise ratio, (SNR) and spatial resolution. First, it is found that an arterial spin labeling (ASL) contribution causes large negative VASO signal changes at short TR. Second, even at high fMRI spatial resolution, CSF volume contributions (7-13%) cause VASO signal changes to become more negative, most noticeably at long TR and TE. Third, white matter (WM) effects reduce signal changes at lower spatial resolution. The VASO technique has been tested using different stimulus paradigms and field strengths (1-3), giving results consistent with comparable tasks investigated using BOLD and cerebral blood flow (CBF)-based techniques. Finally, simulations show that a mixture of fresh and steady-state blood may significantly alter signal changes at short TR (< or =3 s), permitting larger VASO signal changes than expected under pure steady-state conditions. Thus, many competing effects contribute to VASO contrast and care should be taken during interpretation.

Adult↗

An account of the discrepancy between MRI and PET cerebral blood flow measures. A high-field MRI investigation.

There is controversy concerning the discrepancy between absolute cerebral blood flow (CBF) values measured using positron emission tomography (PET) and magnetic resonance imaging (MRI). To gain insight into this problem, the increased signal-to-noise ratio (SNR) and extended T(1) relaxation times of blood and tissue at 3.0 T were exploited to perform pulsed arterial spin labeling (PASL) MRI measurements as a function of spatial resolution and post-labeling delay. The results indicate that, when using post-labeling delays shorter than 1500 ms, MRI gray matter flow values may become as high as several times the correct CBF values owing to tissue signal contamination by remaining arterial blood water label. For delays above 1500 ms, regional PASL-based CBF values (n = 5; frontal gray matter: 48.8 +/- 3.3(SD) ml/100 g/min; occipital gray matter: 49.3 +/- 4.5 ml/100 g/min) comparable with PET-based measurements can be obtained by using spatial resolutions comparable with PET (5-7.5 mm in-plane). At very high resolution (2.5 x 2.5 x 3 mm(3)), gray matter CBF values were found to increase by 10-20%, a consequence attributed to reduction in partial volume effects with cerebrospinal fluid and white matter. The recent availability of MRI field strengths of 3.0 T and higher will facilitate the use of MRI-based CBF measurements in the clinic.

Blood Flow Velocity↗

Retinotopic mapping in the human visual cortex using vascular space occupancy-dependent functional magnetic resonance imaging.

Recently, we introduced a new methodology, vascular space occupancy functional magnetic resonance imaging, which detects brain activation on the basis of blood volume changes in parenchymal microvasculature and may provide higher spatial specificity than the blood oxygenation level-dependent method. To study whether this technique can be used for advanced brain mapping applications, we performed retinotopic mapping using alternating horizontal and vertical wedges that stimulate different portions of the visual field. The results using vascular space occupancy functional magnetic resonance imaging showed clear boundaries for V1/V2/VP/V4v in the ventral areas and V1/V2/V3/V3A in the dorsal areas, similar to the maps obtained using blood oxygenation level-dependent functional magnetic resonance imaging. Vascular space occupancy functional magnetic resonance imaging is a useful addition to the other neuroimaging techniques. Disadvantages of vascular space occupancy functional magnetic resonance imaging include lower contrast-to-noise ratio (about 1/3 of that of blood oxygenation level-dependent method) and limited volume coverage (nine slices for TR=3 s).

Adult↗

Pediatric diffusion tensor imaging: normal database and observation of the white matter maturation in early childhood.

Recent advances in diffusion tensor imaging (DTI) have made it possible to reveal white matter anatomy and to detect neurological abnormalities in children. However, the clinical use of this technique is hampered by the lack of a normal standard of reference. The goal of this study was to initiate the establishment of a database of DTI images in children, which can be used as a normal standard of reference for diagnosis of pediatric neurological abnormalities. Seven pediatric volunteers and 23 pediatric patients (age range: 0-54 months) referred for clinical MR examinations, but whose brains were shown to be normal, underwent anatomical and DTI acquisitions on a 1.5 T MR scanner. The white matter maturation, as observed on DTI color maps, was described and illustrated. Changes in diffusion fractional anisotropy (FA), average apparent diffusion constant (ADC(ave)), and T2-weighted (T2W) signal intensity were quantified in 12 locations to characterize the anatomical variability of the maturation process. Almost all prominent white matter tracts could be identified from birth, although their anisotropy was often low. The evolution of FA, shape, and size of the white matter tracts comprised generally three phases: rapid changes during the first 12 months; slow modifications during the second year; and relative stability after 24 months. The time courses of FA, ADC(ave), and T2W signal intensity confirmed our visual observations that maturation of the white matter and the normality of its architecture can be assessed with DTI in young children. The database is available online and is expected to foster the use of this promising technique in the diagnosis of pediatric pathologies.

Brain↗

DTI tractography based parcellation of white matter: application to the mid-sagittal morphology of corpus callosum.

Morphology of the corpus callosum (CC) at the mid-sagittal level has been a target of extensive studies. However, the lack of internal structures and its polymorphism make it a challenging task to quantitatively analyze shape differences among subjects. In this paper, diffusion tensor Imaging (DTI) and tract tracing technique were applied to incorporate cortical connectivity information to the morphological study. The CC was parcellated into six major subdivisions based on trajectories to different cortical areas. This subdivision was performed for eight normal subjects and one stroke patient. The parcellated CCs of the normal subjects were normalized for morphological analysis. When comparing the stroke patient to the normal population, we detected significant atrophy in the motor and sensory areas of the patient CC, in line with the clinical deficits. This approach provides a new tool to investigate callosal morphology and functional relationships.

Adult↗

Routine clinical brain MRI sequences for use at 3.0 Tesla.

PURPOSE: To establish image parameters for some routine clinical brain MRI pulse sequences at 3.0 T with the goal of maintaining, as much as possible, the well-characterized 1.5-T image contrast characteristics for daily clinical diagnosis, while benefiting from the increased signal to noise at higher field. MATERIALS AND METHODS: A total of 10 healthy subjects were scanned on 1.5-T and 3.0-T systems for T(1) and T(2) relaxation time measurements of major gray and white matter structures. The relaxation times were subsequently used to determine 3.0-T acquisition parameters for spin-echo (SE), T(1)-weighted, fast spin echo (FSE) or turbo spin echo (TSE), T(2)-weighted, and fluid-attenuated inversion recovery (FLAIR) pulse sequences that give image characteristics comparable to 1.5 T, to facilitate routine clinical diagnostics. Application of the routine clinical sequences was performed in 10 subjects, five normal subjects and five patients with various pathologies. RESULTS: T(1) and T(2) relaxation times were, respectively, 14% to 30% longer and 12% to 19% shorter at 3.0 T when compared to the values at 1.5 T, depending on the region evaluated. When using appropriate parameters, routine clinical images acquired at 3.0 T showed similar image characteristics to those obtained at 1.5 T, but with higher signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), which can be used to reduce the number of averages and scan times. Recommended imaging parameters for these sequences are provided. CONCLUSION: When parameters are adjusted for changes in relaxation rates, routine clinical scans at 3.0 T can provide similar image appearance as 1.5 T, but with superior image quality and/or increased speed.

Brain↗

The interaction between magnetization transfer and blood-oxygen-level-dependent effects.

Low-power off-resonance spin-echo magnetization transfer (MT) imaging experiments with a long repetition time (TR) were performed on rat brain for a range of arterial PCO2 levels. The measured magnetization transfer ratio decreased with increased arterial PCO2 levels. When performing blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI)-type data analysis in which signal intensities were normalized to the normocapnic state, the CO2-based BOLD effect was much stronger with than without saturation. This increased effect is a consequence of the fact that the MT effect reduces the signal intensity in tissue more than in blood, thereby amplifying the contribution of the intravascular BOLD signal change to the overall BOLD effect. The results offer a potential approach to measure absolute cerebral blood volume in vivo and to amplify the BOLD effects for fMRI studies.

Animals↗

Experimental measurement of extravascular parenchymal BOLD effects and tissue oxygen extraction fractions using multi-echo VASO fMRI at 1.5 and 3.0 T.

Quantitative interpretation of BOLD fMRI signal changes has predominantly employed empirical models for the whole parenchyma and a calibration step is usually needed to determine the physiological parameters during activation. Although analytical expressions are available for the extravascular and intravascular components of the BOLD effects, it is difficult to experimentally separate tissue from blood signal contributions at the low magnetic fields in which most fMRI studies are performed. Even if this can be achieved, an additional problem that remains is the separation of two types of extravascular BOLD effects, namely those around microvasculature (in the parenchyma close to the site of activation) and those around draining macrovasculature (e.g., in tissue and CSF more remote from the site of activation). In the recently developed vascular space occupancy technique, blood signals are nulled and the activations are localized predominantly in gray matter, allowing experimental measurement of parenchymal extravascular R(2)* and its changes accompanying activation. When comparing such data with total parenchymal R(2)* changes in BOLD fMRI, the extravascular fractions were found to be 47 +/- 7% (mean +/- SEM, n = 4) and 67 +/- 6% at 1.5 and 3.0 T, respectively, in line with expectations that intravascular BOLD contributions are reduced at higher field. The present approach provides a noninvasive means to determine parenchymal oxygen extraction fraction (OEF) in situ. During visual stimulation, OEF values measured at 1.5 and 3.0 T were in good agreement, giving 0.23 +/- 0.01 and 0.21 +/- 0.01, respectively.

Brain↗

Suppression of lipid artifacts in amide proton transfer imaging.

Amide proton transfer (APT) imaging is a type of chemical exchange saturation transfer imaging in which the amide protons of cellular proteins and peptides are saturated and detected via the water resonance. To study this effect, conventional magnetization transfer and direct saturation effects in the frequency-dependent water saturation spectrum (z-spectrum) need to be removed by asymmetry analysis with respect to the water frequency offset. When using echo planar imaging, it was found that unequal pericranial fat saturation at equidistant higher and lower frequencies with respect to water leads to a lipid artifact in APT asymmetry images. It is demonstrated that a chemical-shift-selective refocusing pulse in combination with crusher gradients can suppress this artifact and provide high-quality images.

Amides↗