Faculty Bibliography

The visual system evolved to process natural images, and the goal of visual neuroscience is to understand the computations it uses to do this. Indeed the goal of any theory of visual function is a model that will predict responses to any stimulus, including natural scenes. It has, however, recently become common to take this fundamental principle one step further: trying to use photographic or cinematographic representations of natural scenes (natural stimuli) as primary probes to explore visual computations. This approach is both challenging and controversial, and we argue that this use of natural images is so fraught with difficulty that it is not useful. Traditional methods for exploring visual computations that use artificial stimuli with carefully selected properties have been and continue to be the most effective tools for visual neuroscience. The proper use of natural stimuli is to test models based on responses to these synthetic stimuli, not to replace them

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

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that is the most common cause of nontraumatic disability in young adults in the United States. In recent years, magnetic resonance imaging (MRI) has been established as an important paraclinical tool in MS for the assessment of clinical diagnosis, natural history, and treatment effects. In MS studies, there are many advantages to having a sensitive and reliable in vivo method for investigating the specific pathological changes of white matter and its integrity during the disease process. As a consequence, in the past decade, the application of MRI to the study of MS has been explored from conventional MRI to new advanced quantitative techniques with greater pathological specificity and sensitivity. Diffusion tensor imaging (DTI) is one of the most promising techniques with regard to MS. It quantifies the amount of nonrandom water diffusion within tissues and provides unique in vivo information about the pathological processes that affect water diffusion as a result of brain microstructural damage. This review outlines the current state of the art and future direction of DTI and fiber tractography in the study of MS disease

PURPOSE: To retrospectively assess the importance and imaging appearance of small (< or = 20 mm in diameter) hepatic arterial phase-enhancing (HAPE) lesions that are occult during portal and/or equilibrium phases and at unenhanced T1- and T2-weighted magnetic resonance (MR) imaging and to determine the gross pathologic diagnosis with whole-liver explant comparison. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and compliant with HIPPA. Forty-six patients with cirrhosis who underwent MR imaging and transplantation within 90 days were evaluated with breath-hold T2-weighted and volumetric three-dimensional gadolinium-enhanced gradient-echo MR imaging in the hepatic arterial, portal venous, and equilibrium phases at 1.5 T. Three readers, who were blinded to the pathologic results, retrospectively reviewed the MR images in consensus for small HAPE nodules that were occult at T2-weighted and portal and/or equilibrium phase MR imaging. Only patients with nodules that enhanced during the arterial phase were included in the final study group, which included 16 patients (12 men and four women) aged 18-66 years (median age, 51.5 years). Explanted livers were serially sliced into 5-8-mm-thick sections to evaluate dysplastic nodules and hepatocellular carcinomas (HCCs). The Fisher exact test was performed to determine whether there was a relationship between HCC and the presence of a neoplastic HAPE-only lesion. The Mann-Whitney test was used to determine if patients with at least one neoplastic HAPE-only lesion had a larger number of non-HAPE-only lesions. RESULTS: The 16 patients had 45 HAPE-only lesions; three (7%) of which were neoplastic, including one overt HCC, one HCC arising in a dysplastic nodule, and one dysplastic nodule. None of the remaining 42 HAPE-only lesions (93%) had correlative pathologic findings. All three neoplastic lesions seen only during the arterial phase were found in eight patients with concomitant HCC, who also had an additional 13 pathologically proved nonneoplastic HAPE-only lesions. In eight patients without HCC, none of the HAPE-only lesions were neoplastic. A concomitant non-HAPE-only neoplastic lesion was not a significant (P = .2) predictor for the presence of at least one neoplastic HAPE-only lesion. There was a preliminary but insignificant (P = .13) indication that the number of non-HAPE-only lesions tends to be higher in patients with neoplastic HAPE-only lesions. CONCLUSION: The majority (93%) of HAPE-only lesions that are occult at T2-weighted and portal and/or equilibrium phase MR imaging are nonneoplastic, even in patients with pathologically proved HCC

Myocardial perfusion can be estimated, in principle, from first-pass MR images by converting the T(1)-weighted signal-time curves to contrast agent concentration-time curves. Typically, T(1) weighting is achieved by saturating the magnetization with a nonselective radiofrequency (RF) pulse prior to the imaging sequence. The accuracy of the perfusion estimate derived from the single-point T(1)-weighted signal depends on the initial residual longitudinal magnetization (RLM) produced by the saturation pulse. In this study we demonstrate that single-shot, echo-planar imaging can be used to show initial RLM resulting from incomplete saturation due to static magnetic field and RF field inhomogeneities in the heart at 1.5 T. Three saturation pulses, single, composite simple, and composite B(1)-insensitive rotation (BIR-4) were evaluated in phantom and cardiac experiments. The RLM image was calculated by normalizing the saturated image by a proton-density-weighted image. Mean RLM produced by the three saturation pulses was significantly different in noncontrast cardiac imaging (RLM(single) = 0.108 +/- 0.078; RLM(composite) = 0.051 +/- 0.052; RLM(BIR-4) = 0.011 +/- 0.009; P < 0.001; n = 20). Using a BIR-4 pulse to perform saturation of magnetization seems promising for improving the effectiveness and uniformity of T(1) weighting for first-pass perfusion imaging

A ubiquitous feature of the vertebrate anatomy is the segregation of the brain into white and gray matter. Assuming that evolution maximized brain functionality, what is the reason for such segregation? To answer this question, we posit that brain functionality requires high interconnectivity and short conduction delays. Based on this assumption we searched for the optimal brain architecture by comparing different candidate designs. We found that the optimal design depends on the number of neurons, interneuronal connectivity, and axon diameter. In particular, the requirement to connect neurons with many fast axons drives the segregation of the brain into white and gray matter. These results provide a possible explanation for the structure of various regions of the vertebrate brain, such as the mammalian neocortex and neostriatum, the avian telencephalon, and the spinal cord.

Increasing evidence suggests that oxidative injury is involved in the pathogenesis of many age-related neurodegenerative disorders, including Alzheimer's disease (AD). Identifying the protein targets of oxidative stress is critical to determine which proteins may be responsible for the neuronal impairments and subsequent cell death that occurs in AD. In this study, we have applied a high-throughput shotgun proteomic approach to identify the targets of protein carbonylation in both aged and PS1 + AbetaPP transgenic mice. However, because of the inherent difficulties associated with proteomic database searching algorithms, several newly developed bioinformatic tools were implemented to ascertain a probability-based discernment between correct protein assignments and false identifications to improve the accuracy of protein identification. Assigning a probability to each identified peptide/protein allows one to objectively monitor the expression and relative abundance of particular proteins from diverse samples, including tissue from transgenic mice of mixed genetic backgrounds. This robust bioinformatic approach also permits the comparison of proteomic data generated by different laboratories since it is instrument- and database-independent. Applying these statistical models to our initial studies, we detected a total of 117 oxidatively modified (carbonylated) proteins, 59 of which were specifically associated with PS1 + AbetaPP mice. Pathways and network component analyses suggest that there are three major protein networks that could be potentially altered in PS1 + AbetaPP mice as a result of oxidative modifications. These pathways are 1) iNOS-integrin signaling pathway, 2) CRE/CBP transcription regulation and 3) rab-lyst vesicular trafficking. We believe the results of these studies will help establish an initial AD database of oxidatively modified proteins and provide a foundation for the design of future hypothesis driven research in the areas of aging and neurodegeneration

Nervous systems often face the problem of classifying stimuli and making decisions based on these classifications. The neurons involved in these tasks can be characterized as sensory or motor, according to their correlation with sensory stimulus or motor response. In this study we define a third class of neurons responsible for making perceptual decisions. Our mathematical formalism enables the weighting of neuronal units according to their contribution to decision making, thus narrowing the field for more detailed studies of underlying mechanisms. We develop two definitions of a contribution to decision making. The first definition states that decision making activity can be found at the points of emergence for behavioral correlations in the system. The second definition involves the study of propagation of noise in the network. The latter definition is shown to be equivalent to the first one in the cases when they can be compared. Our results suggest a new approach to analyzing decision making networks.