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Purpose: To develop a method for targeted volumetric, three directional cine phase contrast (PC) imaging with high spatial resolution in clinically feasible scan times., Materials and Methods: A hybrid radial-Cartesian k-space trajectory is used for cardiac gated, volumetric imaging with three directional velocity encoding. Imaging times are reduced by radial undersampling and temporal viewsharing. Phase contrast angiograms are displayed in a new approach that addresses the concern of signal drop out in regions of slow flow. The feasibility of the PC stack of stars (SOS) trajectory was demonstrated with an in vivo study capturing 14 small intracranial aneurysms (2-10 mm). Aneurysm measures from six aneurysms also imaged with digital subtraction angiography (DSA) were compared with linear regression with those from the PC SOS images., Results: All aneurysms were identified on the phase contrast angiograms. The geometric measures from PC SOS and DSA were in good agreement (linear regression: slope = 0.89, intercept = 0.35, R∧2 = 0.88)., Conclusion: PC SOS is a promising method for obtaining volumetric angiograms and cine phase contrast velocity measurements in three dimensions. Acquired spatial resolutions of 0.4 × 0.4 × (0.7-1.0) mm make this method especially promising for studying flow in small intracranial aneurysms., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: To investigate the feasibility of using time-of-flight (TOF) images as a constraint in the reconstruction of a series of highly undersampled time-resolved contrast-enhanced MR images (HYPR TOF), to allow simultaneously high temporal and spatial resolution and increased SNR., Materials and Methods: Ten healthy volunteers and three patients with aneurysms underwent a HYPR TOF study, which includes a clinical routine TOF scan followed by a first pass time-resolved contrast-enhanced exam using an undersampled three-dimensional (3D) projection trajectory (VIPR). Image quality, waveform fidelity and signal to background variation ratio measurements were compared between HYPR TOF images and VIPR images without HYPR reconstruction., Results: Volunteer results demonstrated the feasibility of using the clinical routine TOF as the spatial constraint to reconstruct the first pass time-resolved contrast-enhanced MRA acquired using highly undersampled 3D projection trajectory (VIPR). All the HYPR TOF images are superior to the corresponding VIPR images with the same temporal reconstruction window on both spatial resolution and SNR., Conclusion: HYPR TOF improves the spatial resolution and SNR of the rapidly acquired dynamic images without losing the temporal information., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: To evaluate a novel time-resolved contrast-enhanced (CE) projection reconstruction (PR) magnetic resonance angiography (MRA) method for identifying potential bypass graft target vessels in patients with Class II-IV peripheral vascular disease., Materials and Methods: Twenty patients (M:F = 15:5, mean age = 58 years, range = 48-83 years), were recruited from routine MRA referrals. All imaging was performed on a 1.5 T MRI system with fast gradients (Signa LX; GE Healthcare, Waukesha, WI). Images were acquired with a novel technique that combined undersampled PR with a time-resolved acquisition to yield an MRA method with high temporal and spatial resolution. The method is called PR hyper time-resolved imaging of contrast kinetics (PR-hyperTRICKS). Quantitative and qualitative analyses were used to compare two-dimensional (2D) time-of-flight (TOF) and PR-hyperTRICKS in 13 arterial segments per lower extremity. Statistical analysis was performed with the Wilcoxon signed-rank test., Results: Fifteen percent (77/517) of the vessels were scored as missing or nondiagnostic with 2D TOF, but were scored as diagnostic with PR-hyperTRICKS. Image quality was superior with PR-hyperTRICKS vs. 2D TOF (on a four-point scale, mean rank = 3.3 +/- 1.2 vs. 2.9 +/- 1.2, P < 0.0001). PR-hyperTRICKS produced images with high contrast-to-noise ratios (CNR) and high spatial and temporal resolution. 2D TOF images were of inferior quality due to moderate spatial resolution, inferior CNR, greater flow-related artifacts, and absence of temporal resolution., Conclusion: PR-hyperTRICKS provides superior preoperative assessment of lower limb ischemia compared to 2D TOF.

In contrast-enhanced (CE) magnetic resonance (MR) angiography (MRA), lower injection rates of a fixed contrast agent dose provide longer contrast agent bolus at the expense of lower intravascular signal. This study evaluated the effect of different injection rates in imaging of the vasculature of the lower extremities with time-resolved, CE MRA. In three volunteers, injection rates of 0.5, 1.5 and 3.0 mL/second were administered in a randomized order and imaged in two separate sessions. Contrast agent bolus dynamics measured in volunteers were used in computer simulations to confirm variations in contrast agent concentration as a source of vessel ringing and blurring artifacts. To validate the effect of injection rate in pathologic vessels, 37 patients with peripheral vascular disease were imaged with a time-resolved technique using an injection rate of 0.5 mL/second or 1.5 mL/second and retrospectively divided into two groups. In volunteers, higher injection rates caused a stronger modulation of k-space and resulted in increased ringing artifacts in time-resolved CE MRA. These results were reproduced with computer simulations. In the qualitative patient study, significantly less vessel blurring was observed using a lower injection-rate, without a significant loss of vessel contrast., (Copyright 2001 Wiley-Liss, Inc.)

The purpose of this study was to investigate the effect on three-dimensional (3D) magnetic resonance digital subtraction angiography (MR DSA) images of various injection protocol parameters (ie, injection order, volume, and rate), as well as image masking. The pelves of 10 normal volunteers were scanned using seven different contrast agent volume/injection rate combinations. Subtraction of a precontrast mask image resulted in vascular image contrast improvements of between 4.0 and 7.7 times. Image quality and smaller vessel image contrast in the masked data decreased with increasing injection number. Data acquired with a high (0.150 mmol kg(-1)) volume yielded the highest quality images, although only small nonsignificant differences in image quality and large vessel conspicuity were found between images obtained using the high and medium (0.075 mmol kg(-1)) volumes. Images acquired with a low (0. 038 mmol kg(-1)) volume, while of lower image contrast, were judged to be of reasonable quality, especially when acquired as the first or second injection. Injection rate (1 ml s(-1), 2 ml s(-1), and 4 ml s(-1)) was not found to affect the images significantly, although selection of an injection rate that gave an injection duration of approximately 10 seconds tended to give better vascular image contrast. Based on these data, a series of escalating volumes for multi-injection examination is proposed. J. Magn. Reson. Imaging 2000;12:476-487., (Copyright 2000 Wiley-Liss, Inc.)

With contrast-enhanced MR angiographic techniques, a T1-shortening contrast agent is injected into the blood stream. Imaging during the first pass of the contrast agent permits acquisition of a high-contrast MR angiogram. Scan parameters such as flip angle, repetition time, echo time, and scan duration, and injection parameters, such as dose and rate, must be carefully chosen to achieve maximum contrast between blood vessels and stationary tissues. A critical parameter affecting image quality is the timing of the acquisition relative to the injection. If the collection of the center of k-space does not coincide with peak arterial concentration, artifacts, reduced SNR, and venous enhancement may result. Several techniques have been developed to address the timing issue. Post-processing techniques such as subtracting a pre-contrast image from a post-contrast angiogram can be used to improve image quality. Intravascular contrast agents that may also lead to improved image quality are currently being developed.

Sensory ganglia that innervate taste buds and gustatory papillae (geniculate and petrosal) are reduced in volume by about 40% in mice with a targeted deletion of the gene for brain-derived neurotrophic factor (BDNF). In contrast, the trigeminal ganglion, which innervates papillae but not taste buds on the anterior tongue, is reduced by only about 18%. These specific alterations in ganglia that innervate taste organs make possible a test for roles of lingual innervation in the development of appropriate number, morphology, and spatial pattern of fungiform and circumvallate papillae and associated taste buds. We studied tongues of BDNF null mutant and wild-type littermates and made quantitative analyses of all fungiform papillae on the anterior tongue, the single circumvallate papilla on the posterior tongue, and all taste buds in both papilla types. Fungiform papillae and taste buds were reduced in number by about 60% and were substantially smaller in diameter in mutant mice 15-25 days postnatal. Remaining fungiform papillae were selectively concentrated in the tongue tip region. The circumvallate papilla was reduced in diameter and length by about 40%, and papilla morphology was disrupted. Taste bud number in the circumvallate was reduced by about 70% in mutant tongues, and the remaining taste buds were smaller than those on wild-type tongues. Our results demonstrate a selective dependence of taste organs on a full complement of appropriate innervation for normal growth and morphogenesis. Effects on papillae are not random but are more pronounced in specific lingual regions. Although the geniculate and petrosal ganglia sustain at least half of their normal complement of cell number in BDNF -/- mice, remaining ganglion cells do not substitute for lost neurons to rescue taste organs at control numbers. Whereas gustatory ganglia and the taste papillae initially form independently, our results suggest interdependence in later development because ganglia derive BDNF support from target organs and papillae require sensory innervation for morphogenesis.

The sensitivities of phase-difference (PD) and complex-difference (CD) processing strategies to in-plane motion were examined theoretically and experimentally. Errors in velocity and volume flow rate (VFR) estimates were attributed to (a) motion between different velocity encodings and, in the case of segmented k-space acquisition strategies, (b) motion over the segment duration. PD estimates were found to be insensitive to in-plane motion between velocity encodings, whereas CD VFR estimates were found to be sensitive to this motion. PD estimates, however, were affected by partial volume effects. A corrected CD (CD') scheme was developed that minimizes both partial-volume and in-plane motion effects. Segmented k-space acquisitions with sequential offset and sequential interleaved offset (or centric) phase-encoding schemes were studied. Images obtained using these techniques were found to include both blurring and replication artifacts. The amount of artifact generally increased with the number of views per segment (vps) and the in-plane velocity. PD, CD, and CD' VFR estimates were found to be degraded by these artifacts. The sequential offset phase-encoding scheme generally had acceptable VFR errors (at 4 vps. a CD' VFR error of 7.0%) when averaged over the physiologic range of myocardial motion (> 12 cm second-1); however, larger errors were observed outside this range. VFR estimates obtained using the sequential interleaved phase-encoding scheme at 4 vps were unacceptable. More accurate VFR measurements were obtained using a revised segmented PC strategy, which reversed the order in which the velocity and phase encodings were interleaved. The weighted average CD' VFR error obtained using the revised strategy was 24.5% (for 4 vps). Using displacement information obtained from the two velocity-encoded images, an estimate of the in-plane velocity was obtained and used to correct the acquired data. This decreased the VFR error (weighted average CD' error at 4 vps decreased from 24.5% to -6.3%); however, the implemented correction algorithm could potentially introduced other artifacts in the images.

Taste buds on the mammalian tongue are confined to the epithelium of three types of gustatory papillae: the fungiform, circumvallate, and foliate. The gustatory papillae are composed of an epithelium that covers a broad connective tissue core, with extensive innervation to taste bud and nongustatory epithelial locations. Although the temporal sequence of gustatory papilla development is known for several species, factors that regulate initiation, growth, and maintenance of the papillae are not understood. We tested the hypothesis that sensory innervation is required for the initial formation and early morphogenesis of fungiform papillae in a patterned array. An organ culture of the embryonic rat tongue was developed to provide an in vitro system for studying mechanisms involved in fungiform papilla morphogenesis in patterns on the anterior tongue. Tongues were dissected from embryos at 13 days of gestation (E13), a time when the tongue has not yet fully formed and gustatory papillae have not yet appeared, and at 14 days of gestation (E14), when the tongue is well formed and papillae make their initial morphological appearance. Dissected tongues were maintained at the gas/liquid interface in standard organ culture dishes, fed with DMEM/F12 plus 2% B-27 supplement and 1% fetal bovine serum. After 1, 2, 3, or 6 days in culture, tongues were processed for scanning electron or light microscopy, or immunocytochemistry. Tongues cultured from E13 or E14 underwent extensive morphogenesis and growth in vitro. Furthermore, fungiform papillae developed on these tongues on a culture day equivalent to E15 in vivo; that is, after 2 days for cultures begun at E13 and 1 day for those begun at E14. Because E15 is the characteristic time for gustatory papilla formation in the intact embryo, results demonstrate that the cultured tongues retain important temporal information related to papilla development. In addition, fungiform papillae formed in the tongue cultures in the stereotypic pattern of rows. The papillae were large structures with epithelial and mesenchymal cell integrity, and an intact epithelial basement membrane was indicated with laminin immunoreactivity. The cultures demonstrate that gustatory papilla morphogenesis can progress in the absence of an intact sensory innervation. To exclude a potential developmental role for autonomic ganglion cells that are located in the posterior rat tongue, cultures consisting of only the anterior half of E14 tongues were established. Fungiform papilla development progressed in half tongues in a manner directly comparable to whole tongue cultures. Therefore, robust, reproducible development of fungiform papillae in patterns is supported in rat tongue cultures from E13 or E14, without inclusion of intact sensory or major, posterior tongue autonomic ganglia. This is direct evidence that papillae will form and develop further in vitro without sensory ganglion support. The data also provide the first detailed account of in vitro development of the entire embryonic tongue.

Gustatory papillae are complex organs that are composed of 1) an epithelium, 2) specialized sensory cells within the epithelium (the taste buds), 3) a broad connective core, and 4) sensory innervation. During papilla development, cells in the various tissue compartments must divide, aggregate, detach, migrate, and reaggregate in relation to each other, but factors that regulate such steps are poorly understood and have not been extensively studied. All of these processes potentially require participation of the extracellular matrix. Therefore, we have studied temporal and spatial patterns of immunoreactivity for two extracellular matrix molecules, tenascin and laminin, in the developing fungiform and circumvallate papillae of fetal, perinatal, and adult sheep tongue. To determine relations of tenascin and laminin to sensory innervation, we used an antibody to growth-associated protein (GAP-43) to label growing nerves. Immunocytochemical distributions of tenascin and laminin alter during development in a manner that reflects morphogenesis rather than histologic boundaries of the taste papillae. In early fungiform papillae, tenascin immunoreactivity is very weak within the mesenchyme of the papilla core. However, there is a subsequent shift to an intense, restricted localization in the apical papilla core only--directly under taste bud-bearing regions of the papilla epithelium. In early circumvallate papillae, tenascin immunoreactivity is patchy within the papilla core and within the flanking, nongustatory papillae. Later, immunoreactivity is restricted to the perimeter of the central papilla core, under epithelium that contains developing taste buds. In fungiform and circumvallate papillae, the shift in tenascin immunolocalization is associated with periods of taste bud formation and multiplication within the papilla epithelium and with extensive branching of the sensory innervation in the papilla apex. Laminin immunoreactivity, although it is continuous throughout the basement membrane of general lingual epithelium, is interrupted in the epithelial basement membrane of early fungiform and circumvallate papillae in regions where taste buds are forming. The breaks are large in young fetuses, when taste buds first develop, and are evidenced later as punctate disruptions. Heparan sulfate proteoglycan immunoreactivity confirms that these are basement membrane discontinuities. GAP-43 label coincides with innervation of the papilla core and is most extensive in regions where tenascin immunoreactivity is weak or absent. GAP-43 immunoreactivity is also found in early taste buds: Later, it is extensive within more mature multiple taste buds, presumably in relation to synaptogenesis. We propose that tenascin has a role in promoting deadhesion of cells in the papilla epithelium during periods of taste bud formation and multiplication. Discontinuities in the epithelial basement membrane under developing taste buds, indicated with laminin and heparan sulfate proteoglycan immunoreactivity, may interact to facilitate taste bud morphogenesis and multiplication, to permit access of papilla innervation to the forming taste buds, and/or to allow epithelial/mesenchymal interactions during papilla and taste bud development.

We have previously reported on a complex-difference (CD) flow measurement technique that produces more accurate results than the phase-difference (PD) flow measurement technique due to the greater immunity of the former method to partial volume effects. We report here on some of the ways in which through-plane myocardial motion affects the accuracy of absolute coronary artery flow measurements obtained using the PD and CD techniques. We also discuss motion correction schemes that can be applied to the PD and CD processing methods to improve their accuracy. Computer simulations have been performed to assess the magnitude of the errors associated with these flow measurement techniques when they are applied to small vessels that are attached to a moving background. Laminar and plug flow, with and without complete background suppression, have been considered. Experiments with a moving vessel phantom have been conducted to test the performance of the PD and CD flow measurement techniques in circumstances similar to those simulated. The simulations and the experiments showed that, after corrections for through-plane motion are made, the CD method generally yields more accurate flow results than the PD method. As shown by the simulations, however, both methods yield compromised results due to subtle saturation effects that occur when the direction of myocardial motion is opposite the direction of blood flow. Unvalidated PD and CD measurements of coronary artery flow waveforms in human volunteers are presented to illustrate the magnitude of the proposed through-plane motion effects in vivo.

Magnetic resonance (MR) phase-difference methods work well for measuring volumetric flow rates when the vessel diameter is large compared with the in-plane voxel dimensions. For small vessels (eg, coronary arteries), partial-volume effects introduce substantial errors in the measured volume flow rate. To correctly measure flow rates through a voxel, both the fraction of the voxel containing moving spins and the phase shift imparted to those spins must be known. The authors propose a flow measurement method that combines information obtained with both the complex-difference and phase-difference processing techniques and thereby provides the fractional volume occupied by the moving spins and the phase of those spins. The complex-difference flow map method proposed results in improved accuracy of MR phase-contrast flow measurements in the presence of partial-volume effects.

Late fetal through postnatal development in sheep is a period of increasing convergence of afferent taste fibers onto second-order neurons in the nucleus of the solitary tract (NST). To learn whether neuron morphology alters in concert with convergence and neurophysiological development in NST, three-dimensional neuron reconstructions were made of cells in a functionally defined region of gustatory NST from Golgi preparations of the brainstem. Elongate, multipolar, and ovoid neurons were studied in fetuses from 85 days of gestation through the perinatal period (term = 147 days of gestation), to postnatal stages. Somal size and form, and dendritic complexity and extent, increased markedly from 85 to about 110 days of gestation in both of the proposed NST projection neurons, elongate and multipolar. From 130 days of gestation to postnatal ages, growth of dendrites of elongate neurons plateaued or declined, whereas dendrites of multipolar neurons apparently continued to increase in size and extent. In addition, spine density decreased on elongate neurons but remained stable on multipolar neurons. Morphological variables of ovoid cells, proposed interneurons in NST, did not alter over this later period. The data suggest that multipolar, not elongate or ovoid, neurons are logical candidates to receive the increasing afferent fiber input onto NST cells during late gestation. Also, neural activity from taste afferent fibers is more likely to have a role in altering NST neuron morphology at later, rather than earlier, developmental periods.

This article reviews the general characteristics of several vascular imaging modalities with the purpose of identifying the distinguishing features of magnetic resonance (MR) angiography. Brief discussions of conventional x-ray film angiography, intravenous and intraarterial digital subtraction angiography (DSA), duplex and color Doppler flow ultrasound (US), computed tomographic (CT) angiography, transesophageal and intravascular US, angioscopy, and MR angiography are presented. The advantages and disadvantages of each are discussed. The general attributes and image quality features of MR angiography, intraarterial DSA, CT angiography, and US are compared. It is concluded that no single imaging modality will presently suffice for all purposes. Because of its noninvasiveness, rapidly improving image quality, and ability to directly provide velocity information, MR angiography is likely to play a role in an increasing number of clinical applications.

To learn whether neurophysiological taste responses change during structural development of the gustatory system, we recorded from the chorda tympani nerve in rats aged 7 to 92 days after birth. Chemical stimuli applied to the anterior tongue included four monochloride salts, two acids, sucrose, and urea. Responses to all chemicals were obtained as early as 7 days postnatally. Developmental changes in salt, acid, and sucrose responses were observed. Relative to NaCl and LiCl, NH4Cl and KCl gradually decrease in effectiveness as taste stimuli; or, relative to NH4Cl and KCl, NaCl and LiCl become more effective stimuli. These changes are similar to those observed prenatally and postnatally in sheep. Also, relative to NaCl, citric acid, hydrochloric acid, and sucrose become less effective stimuli; or, NaC1 becomes more effective as a stimulus, relative to these acids and sucrose. The period of most rapid functional change overlaps a period of rapid structural change. It seems most reasonable to hypothesize that the altering taste responses reflect developmental changes in receptor membrane composition. Since the taste system is not programmed to respond in a mature manner from the moment function begins, there is ample opportunity for changing taste experience to influence the developing taste system.

There is considerable interest in the use of Doppler catheters for measuring coronary flow reserve in humans. Two types are currently available, these being models having side-mounted or tip-mounted transducers. The performance of these catheters was carefully observed in Silastic tubing perfused with blood by a roller pump. Each catheter was used with two types of positioning wire: a rigid wire and a standard J-tip guidewire. Linear regressions of velocity vs. flow rate were performed. Both catheters performed well with the rigid wire (r greater than or equal to 0.992). When used with the J-tip, the end-mounted catheter suffered decreased performance because of positioning difficulties, while the side-mounted catheter performance was within 6% of the ideal. Measurements made with the side-mounted catheter at low flow rates underestimated the expected response for forward flow. Because of the ease of positioning, the side-mounted catheter is judged to be more useful in measuring flow ratios.

To learn whether salt taste responses change during mammalian development, we recorded from multifiber preparations of the chorda tympani while stimulating the anterior tongue in sheep fetuses, lambs, and adults. Stimuli were 0.5 M NH4Cl, KCl, NaCl, and LiCl, and 0.05-0.75 M concentration series of the first three salts. Ultrastructural studies were made of taste buds at different ages to determine whether morphological elements such as microvilli and tight junctions are present in young fetuses. Substantial changes occur in relative salt taste responses, throughout development. In fetuses that are beginning the last third of gestation, NaCl and LiCl elicit much smaller response magnitudes than NH4Cl and KCl. Throughout the rest of gestation and postnatally, the NaCl and LiCl responses gradually increase in magnitude relative to NH4Cl and KCl. In adults, NaCl, LiCl, and NH4Cl all elicit similar response magnitudes and KCl is less effective as a taste stimulus. At ages when response ratios for the 0.5 M salts are changing, there are no changes in shapes of the response/concentration functions for individual salts. Furthermore, microvilli are present on taste bud cell apices and tight junctions are found between cells in the youngest fetuses studied. Therefore, initial stimulus-receptor membrane contacts are probably similar to those in adults. Our data suggest that different membrane components interact with the various monochloride salts and that taste receptors contain different proportions of these various membrane components at different developmental stages. Therefore young taste bud cells do not have the same salt response characteristics as mature cells, and a changing neural substrate underlies development of salt taste function, both pre- and postnatally.