Faculty Bibliography

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

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

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

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

Mutations in eukaryotic initiation factor 2B (eIF2B) cause one of the most common leukodystrophies, childhood ataxia with CNS hypomyelination/vanishing white matter disease or CACH/VWM. Patients may develop a wide spectrum of neurological abnormalities from prenatal-onset white matter disease to juvenile or adult-onset ataxia and dementia, sometimes with ovarian insufficiency. The pattern of diffuse white matter abnormalities on MRI of the head is often diagnostic. Neuropathological abnormalities indicate a unique and selective disruption of oligodendrocytes and astrocytes with sparing of neurons. Marked decrease of asialo-transferrin in cerebrospinal fluid is the only biochemical abnormality identified thus far. Eukaryotic translation initiation factor 2B (eIF2B) mutations cause a decrease in guanine nucleotide exchange activity on eIF2-GDP, resulting in increased susceptibility to stress and enhanced ATF4 expression during endoplasmic reticulum stress. eIF2B mutations are speculated to lead to increased susceptibility to various physiological stress conditions. Future research will be directed towards understanding why abnormal control of protein translation predominantly affects brain glial cells.

Gli2 and Gli3 are the primary transcription factors that mediate Sonic hedgehog (Shh) signals in the mouse. Gli3 mainly acts as a transcriptional repressor, because the majority of full-length Gli3 protein is proteolytically processed. Gli2 is mostly regarded as a transcriptional activator, even though it is also suggested to have a weak repressing activity. What the molecular basis for its possible dual function is and how its activity is regulated by Shh signaling are largely unknown. Here we demonstrate that unlike the results seen with Gli3 and Cubitus Interruptus, the fly homolog of Gli, only a minor fraction of Gli2 is proteolytically processed to form a transcriptional repressor in vivo and that in addition to being processed, Gli2 full-length protein is readily degraded. The degradation of Gli2 requires the phosphorylation of a cluster of numerous serine residues in its carboxyl terminus by protein kinase A and subsequently by casein kinase 1 and glycogen synthase kinase 3. The phosphorylated Gli2 interacts directly with betaTrCP in the SCF ubiquitin-ligase complex through two binding sites, which results in Gli2 ubiquitination and subsequent degradation by the proteasome. Both processing and degradation of Gli2 are suppressed by Shh signaling in vivo. Our findings provide the first demonstration of a molecular mechanism by which the Gli2 transcriptional activity is regulated by Shh signaling

OBJECTIVE: We optimized a time-resolved 3D contrast-enhanced MR angiography sequence with integrated parallel imaging technique that can provide a large field of view with high temporal and spatial resolution, by which the hemodialysis access and the entire course of the inflow and outflow vessels can be imaged at a single anatomic station. Our objective was to evaluate the feasibility and usefulness of this method in the evaluation of patients referred for possible abnormalities in hemodialysis access. CONCLUSION: Time-resolved contrast-enhanced 3D MR angiography with parallel imaging has the potential to provide a rapid and comprehensive evaluation for the surveillance and diagnosis of hemodialysis access malfunctions. This technique may function as an important complement to conventional digital subtraction angiography and may be able to help guide medical management. The MR angiography protocol we present is a noninvasive, versatile, and time-efficient technique, without the need of direct graft puncture or flow interruption, and can be performed using a single injection of contrast material at a single station

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

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

PURPOSE: To retrospectively assess the usefulness of contrast material-enhanced T1-weighted magnetic resonance (MR) imaging alone and with T2-weighted MR imaging in the diagnosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A waiver of informed consent and institutional review board approval for this retrospective study were granted. The study was HIPAA compliant. Twenty-eight men (mean age, 49 years; range, 23-70 years) and 10 women (mean age, 53 years; range, 42-72 years) with cirrhosis underwent T2-weighted and contrast-enhanced T1-weighted MR imaging at 1.5 T within 90 days of liver transplantation. Three readers reviewed the T1-weighted images alone and then the T2-weighted and T1-weighted images together. Lesion detection, characterization, and reader confidence levels were recorded. RESULTS: At liver explantation, 57 lesions were present in 18 patients: 19 HCCs, 33 dysplastic nodules, and five cysts. Contrast-enhanced T1-weighted imaging depicted 13 of 19 HCCs with an overall sensitivity of 68.4% (13 of 19) and specificity of 65.7% (23 of 35). The sensitivity and specificity for detection of dysplastic nodules (sensitivity, 9%; specificity, 68.4%) and HCCs (sensitivity, 68.4%; specificity, 65.7%) were nearly identical for T1-weighted images read alone or read with T2-weighted images. The only difference was the specificity for T1-weighted images read alone (65.7%) and read with T2-weighted images (62.9%). The addition of T2-weighted images altered the diagnosis in one of 90 (1.1%) cases and provided an increase in diagnostic confidence in four of 258 (1.6%) cases for independent readers and three of 90 (3.3%) cases at consensus reading. CONCLUSION: Contrast-enhanced T1-weighted imaging can be used as a stand-alone sequence for the diagnosis of HCC in patients with cirrhosis prior to liver transplantation