Faculty Bibliography

Cardiovascular MR imaging (CVMR) has become a valuable modality for the non-invasive detection and characterization of cardiovascular diseases. CVMR requires high imaging speed and efficiency, which is fundamentally limited in conventional cardiovascular MRI studies. With the introduction of parallel imaging, alternative means for increasing acquisition speed beyond these limits have become available. In parallel imaging some image data are acquired simultaneously, using RF detector coil sensitivities to encode simultaneous spatial information that complements the information gleaned from sequential application of magnetic field gradients. The resulting improvements in imaging speed can be used in various ways, including shortening long examinations, improving spatial resolution and/or anatomic coverage, improving temporal resolution, enhancing image quality, overcoming physiological constraints, detecting and correcting for physiologic motion, and streamlining work flow. Examples of each of these strategies will be provided in this review. First, basic principles and key concepts of parallel MR are described. Second, practical considerations such as coil array design, coil sensitivity calibrations, customized pulse sequences and tailored imaging parameters are outlined. Next, cardiovascular applications of parallel MR are reviewed, ranging from cardiac anatomical and functional assessment to myocardial perfusion and viability to MR angiography of the coronary arteries and the large vessels. Finally, current trends and future directions in parallel CVMR are considered

Adenoid cystic carcinoma is an indolent, slow-growing tumor that may first cause low-grade pain in the affected region. This article describes a case involving adenoid cystic carcinoma of the maxilla that was present for approximately nine years. Prior to diagnosis, five dentists reported that the patient had anisocoria, migraine headaches, and low-to-moderate upper jaw pain that was refractory to conventional therapy. A surgical resection was performed; after a period of soft tissue healing, radiation therapy was initiated. The surgical defect was obturated using an interim removable prosthesis while awaiting final reconstruction by a maxillofacial prosthodontist. This article examines possible reasons why this lesion was not diagnosed sooner and discusses how this case should raise the general dentist's awareness of such lesions

The mechanisms through which hematopoietic cytokines accelerate revascularization are unknown. Here, we show that the magnitude of cytokine-mediated release of SDF-1 from platelets and the recruitment of nonendothelial CXCR4+ VEGFR1+ hematopoietic progenitors, 'hemangiocytes,' constitute the major determinant of revascularization. Soluble Kit-ligand (sKitL), thrombopoietin (TPO, encoded by Thpo) and, to a lesser extent, erythropoietin (EPO) and granulocyte-macrophage colony-stimulating factor (GM-CSF) induced the release of SDF-1 from platelets, enhancing neovascularization through mobilization of CXCR4+ VEGFR1+ hemangiocytes. Although revascularization of ischemic hindlimbs was partially diminished in mice deficient in both GM-CSF and G-CSF (Csf2-/- Csf3-/-), profound impairment in neovascularization was detected in sKitL-deficient Mmp9-/- as well as thrombocytopenic Thpo-/- and TPO receptor-deficient (Mpl-/-) mice. SDF-1-mediated mobilization and incorporation of hemangiocytes into ischemic limbs were impaired in Thpo-/-, Mpl-/- and Mmp9-/- mice. Transplantation of CXCR4+ VEGFR1+ hemangiocytes into Mmp9-/- mice restored revascularization, whereas inhibition of CXCR4 abrogated cytokine- and VEGF-A-mediated mobilization of CXCR4+ VEGFR1+ cells and suppressed angiogenesis. In conclusion, hematopoietic cytokines, through graded deployment of SDF-1 from platelets, support mobilization and recruitment of CXCR4+ VEGFR1+ hemangiocytes, whereas VEGFR1 is essential for their angiogenic competency for augmenting revascularization. Delivery of SDF-1 may be effective in restoring angiogenesis in individuals with vasculopathies

A method for estimating T1 using a single breath-hold, segmented, inversion recovery prepared, true fast imaging with steady-state precession (sIR-TrueFISP) acquisition at low flip angle (FA) was implemented in this study. T1 values measured by sIR-TrueFISP technique in a Gd-DTPA-doped water phantom and the human brain and abdomen of healthy volunteers were compared with the results of the standard IR fast spin echo (FSE) technique. A good correlation between the two methods was observed (R2=0.999 in the phantom, and R2=0.943 in the brain and abdominal tissues). The T1 values of the tissues agreed well with published results. sIR-TrueFISP enables fast measurements of T1 to be obtained within a single breath-hold with good accuracy, which is particularly important for chest and abdominal imaging

Cytochrome c (CC) immunoreactivity was quantified in functionally distinct rat hippocampal inhibitory neuron populations using double immunocytochemistry and laser scanning confocal microscopy to measure the CC expression level as well as the amount of mitochondria within the cells, which is a sign of neuronal activity. The CC signal showed a similar distribution to cytochrome c oxidase histochemical staining. Strongly stained somata, dendrites and axon terminal clouds were dispersed over the low intensity neuropil staining. The staining was granular and electron microscopic investigation confirmed that the signal was localized in mitochondria. Intensively labeled neurons, showing the morphological features of inhibitory cells, were most frequently found in the principal cell layers, stratum oriens of the CA1-3 areas, stratum lucidum and hilus. These neurons contained not only a higher number of mitochondria than the principal cells but the intensity of the mitochondrial staining was evidently stronger. Among the examined interneuronal populations, parvalbumin-immunoreactive neurons were intensively labeled for CC. Calbindin D28k- (CB), somatostatin- and cholecystokinin-labeled cells showed heterogeneous CC levels, whereas calretinin-immunoreactive cells never showed a strong CC signal. CB cells in stratum oriens and alveus layers, lucidum and the hilus were strongly labeled for CC. CB cells in such regions are known to project to the medial septum and contain somatostatin. We have demonstrated that the CA1 interneurons that project to the medial septum (hippocampo-septal neurons) express a high level of CC. Thus, similar to the parvalbumin-containing basket and axo-axonic cells, the hippocampo-septal neurons potentially have a high average activity level

Although extracellular unit recording is typically used for the detection of spike occurrences, it also has the theoretical ability to report about what are typically considered intracellular features of the action potential. We address this theoretical ability by developing a model system that captures features of experimentally recorded simultaneous intracellular and extracellular recordings of CA1 pyramidal neurons. We use the line source approximation method of Holt and Koch to model the extracellular action potential (EAP) voltage resulting from the spiking activity of individual neurons. We compare the simultaneous intracellular and extracellular recordings of CA1 pyramidal neurons recorded in vivo with model predictions for the same cells reconstructed and simulated with compartmental models. The model accurately reproduces both the waveform and the amplitude of the EAPs, although it was difficult to achieve simultaneous good matches on both the intracellular and extracellular waveforms. This suggests that accounting for the EAP waveform provides a considerable constraint on the overall model. The developed model explains how and why the waveform varies with electrode position relative to the recorded cell. Interestingly, each cell's dendritic morphology had very little impact on the EAP waveform. The model also demonstrates that the varied composition of ionic currents in different cells is reflected in the features of the EAP

We studied the development of visual activation longitudinally in two infant monkeys aged 103-561 days using the BOLD fMRI technique under opiate anesthesia and compared the results with those obtained in three adult animals studied under identical conditions. Visual activation in primary visual cortex, V1, was strong and reliable in monkeys of the youngest and oldest ages, showing that functional imaging techniques give qualitatively similar results in infants and adults. Visual activation in extrastriate areas involved in processing motion (MT/V5) and form (V4) was not evident in the younger animals, but became more adult-like in the older animals. This delayed onset of measurable BOLD responses in extrastriate visual cortex may reflect delayed development of visual responses in these areas, although at this stage it is not possible to rule out either effects of anesthesia or of changes in cerebral vascular response mechanisms as the cause. The demonstration of visually evoked BOLD responses in young monkeys shows that the BOLD fMRI technique can usefully be employed to address functional questions of brain development

Sensory information is encoded by populations of neurons. The responses of individual neurons are inherently noisy, so the brain must interpret this information as reliably as possible. In most situations, the optimal strategy for decoding the population signal is to compute the likelihoods of the stimuli that are consistent with an observed neural response. But it has not been clear how the brain can directly compute likelihoods. Here we present a simple and biologically plausible model that can realize the likelihood function by computing a weighted sum of sensory neuron responses. The model provides the basis for an optimal decoding of sensory information. It explains a variety of psychophysical observations on detection, discrimination and identification, and it also directly predicts the relative contributions that different sensory neurons make to perceptual judgments

Hyperpolarized helium (3He) gas MRI has the potential to assess pulmonary function. The non-equilibrium state of hyperpolarized 3He results in the continual depletion of the signal level over the course of excitations. Under non-equilibrium conditions the relationship between the signal-to-noise ratio (SNR) and the number of excitations significantly deviates from that established in the equilibrium state. In many circumstances the SNR increases or remains the same when the number of data acquisitions decreases. This provides a unique opportunity for performing parallel MRI in such a way that both the temporal and spatial resolution will increase without the conventional decrease in the SNR. In this study an analytical relationship between the SNR and the number of excitations for any flip angle was developed. Second, the point-spread function (PSF) was utilized to quantitatively demonstrate the unconventional SNR behavior for parallel imaging in hyperpolarized gas MRI. Third, a 24-channel (24ch) receive and two-channel (2ch) transmit phased-array system was developed to experimentally prove the theoretical predictions with 3He MRI. The in vivo experimental results prove that significant temporal resolution can be gained without the usual SNR loss in an equilibrium system, and that the entire lung can be scanned within one breath-hold (approximately 13 s) by applying parallel imaging to 3D data acquisition

The midbrain and anterior hindbrain offer an ideal system in which to study the coordination of tissue growth and patterning in three dimensions. Two organizers that control anteroposterior (AP) and dorsoventral (DV) development are known, and the regulation of AP patterning by Fgf8 has been studied in detail. Much less is known about the mechanisms that control mid/hindbrain development along the DV axis. Using a conditional mutagenesis approach, we have determined how the ventrally expressed morphogen sonic hedgehog (Shh) directs mid/hindbrain development over time and space through positive regulation of the Gli activators (GliA) and inhibition of the Gli3 repressor (Gli3R). We have discovered that Gli2A-mediated Shh signaling sequentially induces ventral neurons along the medial to lateral axis, and only before midgestation. Unlike in the spinal cord, Shh signaling plays a major role in patterning of dorsal structures (tectum and cerebellum). This function of Shh signaling involves inhibition of Gli3R and continues after midgestation. Gli3R levels also regulate overall growth of the mid/hindbrain region, and this largely involves the suppression of cell death. Furthermore, inhibition of Gli3R by Shh signaling is required to sustain expression of the AP organizer gene Fgf8. Thus, the precise spatial and temporal regulation of Gli2A and Gli3R by Shh is instrumental in coordinating mid/hindbrain development in three dimensions