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Biomedical subjects

Hanzhang Lu

Publications and source records attributed to Hanzhang Lu.

At least 19 recordsLinked to original sources

Inverse correlation between cerebral blood flow measured by continuous arterial spin-labeling (CASL) MRI and neurocognitive function in children with sickle cell anemia (SCA).

Overt stroke, clinically "silent" cerebral infarct, and neurocognitive impairment are frequent complications of sickle cell anemia (SCA). Current imaging techniques have limited sensitivity and specificity to identify children at risk for neurocognitive impairment. We prospectively evaluated 24 children with SCA with a neurologic exam, complete blood count, transcranial Doppler ultrasound (TCD), measurement of intelligence quotient (IQ), and magnetic resonance imaging (MRI) with measurement of cerebral blood flow (CBF) using continuous arterial spin-labeling (CASL) MRI. Average CBF to gray matter was 112 +/- 36 mL/100 g/min. We identified a strong inverse relationship between performance IQ and CBF (-1.5 points per 10 mL/100 g/min increase in CBF, P = .013). Elevated steady-state white blood cell count (> or = 14 x 10(9)/L [14,000/microL]) was associated with lower full scale IQ (86 +/- 9 vs 99 +/- 10, P = .005). CASL MRI may identify children with neurocognitive impairment, before damage is evident by structural MRI or TCD.

Anemia, Sickle Cell↗

Magnetic field correlation imaging.

A magnetic resonance imaging (MRI) method is presented for estimating the magnetic field correlation (MFC) associated with magnetic field inhomogeneities (MFIs) within biological tissues. The method utilizes asymmetric spin echoes and is based on a detailed theory for the effect of MFIs on nuclear magnetic resonance (NMR) signal decay. The validity of the method is supported with results from phantom experiments at 1.5 and 3 T, and human brain images obtained at 3 T are shown to demonstrate the method's feasibility. The preliminary results suggest that MFC imaging may be useful for the quantitative assessment of iron within the brain.

Algorithms↗

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↗

Microvessel density estimation in the human brain by means of dynamic contrast-enhanced echo-planar imaging.

Animal studies have shown that in vivo estimates of microvessel density in the brain may be obtained from an MRI-measurable index (Q) provided that a sufficiently high dose of an intravascular paramagnetic contrast agent is employed. Q is determined from the shifts in the transverse relaxation rates induced by the contrast agent, and a high dose is required for the validity of analytic expressions relating Q to the microvessel density. However, the steady-state imaging techniques used in these prior investigations are not appropriate for humans, as the required contrast agent dose is too large. Here results of a pilot study with three subjects are reported. The results suggest that reliable Q measurements can be performed in the human brain at 1.5 T by using an interleaved spin-echo (SE)/gradient-echo (GE) echo-planar imaging (EPI) sequence and a bolus injection of a triple dose of Gd-DTPA. Lower- and upper-bound estimates for the microvessel density were derived from the Q-values, and were found to be in reasonable accord with previously cited values determined by histology.

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↗

Three-dimensional characterization of non-gaussian water diffusion in humans using diffusion kurtosis imaging.

Conventional diffusion tensor imaging (DTI) measures water diffusion parameters based on the assumption that the spin displacement distribution is a Gaussian function. However, water movement in biological tissue is often non-Gaussian and this non-Gaussian behavior may contain useful information related to tissue structure and pathophysiology. Here we propose an approach to directly measure the non-Gaussian property of water diffusion, characterized by a four-dimensional matrix referred to as the diffusion kurtosis tensor. This approach does not require the complete measurement of the displacement distribution function and, therefore, is more time efficient compared with the q-space imaging technique. A theoretical framework of the DK calculation is established, and experimental results are presented for humans obtained within a clinically feasible time of about 10 min. The resulting kurtosis maps are shown to be robust and reproducible. Directionally-averaged apparent kurtosis coefficients (AKC, a unitless parameter) are 0.74 +/- 0.03, 1.09 +/- 0.01 and 0.84 +/- 0.02 for gray matter, white matter and thalamus, respectively. The three-dimensional kurtosis angular plots show tissue-specific geometry for different brain regions and demonstrate the potential of identifying multiple fiber structures in a single voxel. Diffusion kurtosis imaging is a useful method to study non-Gaussian diffusion behavior and can provide complementary information to that of DTI.

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↗

Noninvasive quantification of cerebral blood volume in humans during functional activation.

Like cerebral blood flow (CBF), cerebral blood volume (CBV) is an important physiological parameter closely associated with brain activity and thus, noninvasive quantification of CBV during brain activation provides another opportunity to investigate the relationship between neuronal activity and hemodynamic changes. In this paper, a new method is presented that is able to quantify CBV at rest and during activation. Specifically, using an inversion recovery pulse sequence, a set of brain images was collected at various inversion times (TIs). At each TI, functional images were acquired with a block-design visual stimulation paradigm. A biophysical model comprised of multiple tissue components was developed and was utilized for the determination of CBV using the visual stimulation data. MRI experiments on five healthy volunteers showed that CBV was 5.0 +/- 1.5 ml blood/100 ml brain during rest and increased to 6.6 +/- 1.8 ml blood/100 ml brain following visual stimulation. Furthermore, experiments with visual stimulation at two frequencies (2 and 8 Hz) showed that the increases in CBV correlated with the strength of stimulation. This technique, with its ability to measure quantitative CBV values noninvasively, provides a valuable tool for quantifying hemodynamic signals associated with brain activation.

Algorithms↗

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↗

In vivo flow territory mapping of major brain feeding arteries.

The ability to visualize the perfusion territories of major feeding arteries to the brain is important for many clinical applications. Since the work of Duret in 1874 on vascularization of the brain, many textbooks and atlases have shown schematic drawings of the supply areas of the major cerebral arteries. Recent postmortem studies demonstrated that the variability of the cerebral vascular territories is significantly greater than previously assumed. The aim of the present study was to investigate in vivo, the variability of flow territories of major brain feeding arteries. Flow territory mapping of the anterior (internal carotid arteries) and posterior (basilar artery) circulation was performed in 115 (58 +/- 9 years of age) subjects with selective arterial spin labeling MRI. Flow territory maps for the entire population indicated significant variation in flow territories. However, when the subjects are further categorized into groups with a complete circle of Willis, with a missing A1 segment and with a unilateral or bilateral fetal-type posterior cerebral artery, the results showed considerably lower variation within groups. It is therefore concluded that, the variation observed from the entire population is mainly caused by anatomical variants of the circle of Willis. To relate focal brain lesions to underlying flow territories in individual cases, knowledge of the anatomy of the circle of Willis is essential.

Aged↗

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↗

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↗

Diffusional kurtosis imaging: the quantification of non-gaussian water diffusion by means of magnetic resonance imaging.

A magnetic resonance imaging method is presented for quantifying the degree to which water diffusion in biologic tissues is non-Gaussian. Since tissue structure is responsible for the deviation of water diffusion from the Gaussian behavior typically observed in homogeneous solutions, this method provides a specific measure of tissue structure, such as cellular compartments and membranes. The method is an extension of conventional diffusion-weighted imaging that requires the use of somewhat higher b values and a modified image postprocessing procedure. In addition to the diffusion coefficient, the method provides an estimate for the excess kurtosis of the diffusion displacement probability distribution, which is a dimensionless metric of the departure from a Gaussian form. From the study of six healthy adult subjects, the excess diffusional kurtosis is found to be significantly higher in white matter than in gray matter, reflecting the structural differences between these two types of cerebral tissues. Diffusional kurtosis imaging is related to q-space imaging methods, but is less demanding in terms of imaging time, hardware requirements, and postprocessing effort. It may be useful for assessing tissue structure abnormalities associated with a variety of neuropathologies.

Anisotropy↗

Novel approach to the measurement of absolute cerebral blood volume using vascular-space-occupancy magnetic resonance imaging.

Quantitative determination of cerebral blood volume (CBV) is important for understanding brain physiology and pathophysiology. In this work, a novel approach is presented for accurate measurement of absolute CBV (aCBV) using vascular-space-occupancy (VASO) MRI, a blood-nulling pulse sequence, in combination with the T(1) shortening property of Gd-DTPA. Two VASO images with identical imaging parameters are acquired before and after contrast agent injection, resulting in a subtracted image that reflects the amount of blood present in the brain, i.e., CBV. With an additional normalizing factor, aCBV in units of milliliters of blood per 100 mL of brain can be estimated. Experimental results at 1.5 and 3 T systems showed that aCBV maps with high spatial resolution can be obtained with high reproducibility. The averaged aCBV values in gray and white matter were 5.5 +/- 0.2 and 1.4 +/- 0.1 mL of blood/100 mL of brain, respectively. Compared to dynamic susceptibility contrast techniques, VASO MRI is based upon a relatively straightforward theory and the calculation of CBV does not require measurement of an arterial input function. In comparison with previous pre/postcontrast difference approaches, VASO MRI provides maximal signal difference between pre- and postcontrast situation and does not require the use of whole blood for signal normalization.

Adult↗

Flow territory mapping of the cerebral arteries with regional perfusion MRI.

BACKGROUND AND PURPOSE: Conventional contrast-enhanced angiography is the gold standard for visualization of the vascular tree supplied by the major cerebral arteries and assessment of collateral flow. Thus far, however, no methods are available to assess the actual flow territories of the individual cerebral arteries. In the present study, we evaluate a noninvasive arterial spin labeling MRI method for selective mapping of the flow territories of the left and right internal carotid arteries and posterior circulation (basilar artery and vertebral arteries). METHODS: A spatially selective labeling approach, regional perfusion imaging, was developed on the basis of selective slab inversion of the arterial water with a pulsed arterial spin labeling sequence. The selectivity of this method was demonstrated. RESULTS: Regional perfusion imaging enables assessment of the perfusion territories of the major cerebral arteries. With selective labeling of an internal carotid artery, signal is present in both the ipsilateral anterior cerebral artery and ipsilateral middle cerebral artery flow territory. With labeling of the basilar artery, perfusion-weighted signal is symmetrically present in both posterior cerebral artery flow territories. Cerebral blood flow values measured with regional perfusion imaging in the complete hemisphere (40.1 mL x min(-1) x 100 g(-1) tissue), white matter (22.1 mL x min(-1) x 100 g(-1) tissue), and gray matter (65.8 mL x min(-1) x 100 g(-1) tissue) are in agreement with data in the literature. CONCLUSIONS: We present the first imaging method capable of evaluating both quantitatively and qualitatively the flow territories of the individual brain-feeding arteries in vivo.

Adult↗

Multiple acquisitions with global inversion cycling (MAGIC): a multislice technique for vascular-space-occupancy dependent fMRI.

Recently, a new fMRI technique, termed vascular-space-occupancy (VASO), was introduced that uses T1-based blood nulling to detect cerebral blood volume (CBV) changes during brain activity. However, similar to other T1-preparation methods, this technique is hampered by the fact that there is only one zero-crossing on the relaxation curve, presently limiting its application to single-slice studies. A multislice VASO-fMRI method is presented that employs a series of nonselective 180 degrees pulses to periodically invert the magnetization and maintain it around zero, while acquiring slices in between. The effects of magnetization transfer and signal contamination by stimulated echoes are discussed. Solutions to reduce the effect of T1-signal decay as a function of slice number are provided. Phantom data show excellent agreement between experiments and numerical simulations. Multislice VASO-fMRI images of visual stimulation show effective blood nulling in all slices and appropriate functional activations in all volunteers (n=4).

Blood Volume↗

Determining the longitudinal relaxation time (T1) of blood at 3.0 Tesla.

It is important to determine the longitudinal relaxation time of blood for black blood imaging, as well as for quantifying blood flow by arterial spin labeling (ASL). In this study a circulation system was used to measure blood T1 under physiological conditions at the new clinical field strength of 3.0T. It was found that 1/T1 in s(-1) was linearly dependent (P < 0.05) on hematocrit (Hct) within a normal range of 0.38-0.46. The relationships were 1/T1 = (0.52 +/- 0.15). Hct + (0.38 +/- 0.06) and 1/T1 = (0.83 +/- 0.07). Hct + (0.28 +/- 0.03) for arterial (oxygenation = 92% +/- 7%) and venous blood (69% +/- 8%), respectively, which led to estimated T1 values of 1664 +/- 14 ms (arterial) and 1584 +/- 5 ms (venous) at a typical human Hct of 0.42. The temperature dependencies of blood T1 were 22.3 +/- 0.6 ms/ degrees C and 19.8 +/- 0.8 ms/ degrees C for Hct values of 0.42 and 0.38, respectively. When a head coil transmit/receive setup was used, radiation damping caused a slight reduction (19 ms) of the measured T1 values.

Animals↗

Sustained poststimulus elevation in cerebral oxygen utilization after vascular recovery.

The brain's response to functional activation is characterized by focal increases in cerebral blood flow. It is generally assumed that this hyperemia is a direct response to the energy demands of activation, the so-called flow-metabolism coupling. Here we report experimental evidence that increases in oxygen metabolism can occur after activation without increases in flow. When using multimodality functional MRI (fMRI) to study visual activation in human brain, we observed a postactivation period of about 30 seconds during which oxygen consumption remained elevated, while blood flow and volume had already returned to baseline levels. The finding of such a prolonged and complete dissociation of vascular response and energy metabolism during the poststimulus period indicates that increased metabolic demand needs not per se cause a concomitant increase in blood flow. The results also show that the postactivation undershoot after the positive blood-oxygen-level-dependent hemodynamic response in fMRI should be reinterpreted as a continued elevation of oxygen metabolism, rather than a delayed blood volume compliance.

Adult↗