Faculty Bibliography

PURPOSE OF REVIEW: Cystinuria is a rare genetic disease with increased urinary excretion of the poorly soluble amino acid cystine. It can lead to significant morbidity in affected patients due to the often large and recurrent resulting kidney stones. Treatment is focused on the prevention of stone formation. There have been few advances in the available therapeutic options for the disorder in the last 15-20 years. RECENT FINDINGS: Although no new treatments have emerged in the prevention of cystinuria in recent years, several developments hold promise for advancing the field of caring for affected patients. A new method of measuring urinary cystine and estimating potential for stone formation, called cystine capacity, may prove to be a useful tool in monitoring the disease. The discoveries of the mutations that cause cystinuria have led to a new classification system based on genotype that is more accurate than the prior phenotypic one. The finding of new compounds that inhibit cystine crystal growth in vitro, now being tested in animal models, may lead to new potential therapies in years to come. The Rare Kidney Stone Consortium has developed a registry and hopes to lead further efforts in dealing with cystinuria. SUMMARY: With several recent advances in the monitoring and treatment of cystinuria, and the gathering of clinical patient data, there are now opportunities for new management protocols and therapies.

For patients with impaired breath-hold capacity and/or arrhythmias, real-time cine MRI may be more clinically useful than breath-hold cine MRI. However, commercially available real-time cine MRI methods using parallel imaging typically yield relatively poor spatio-temporal resolution due to their low image acquisition speed. We sought to achieve relatively high spatial resolution ( approximately 2.5 x 2.5 mm(2) ) and temporal resolution ( approximately 40 ms), to produce high-quality real-time cine MR images that could be applied clinically for wall motion assessment and measurement of left ventricular function. In this work, we present an eightfold accelerated real-time cardiac cine MRI pulse sequence using a combination of compressed sensing and parallel imaging (k-t SPARSE-SENSE). Compared with reference, breath-hold cine MRI, our eightfold accelerated real-time cine MRI produced significantly worse qualitative grades (1-5 scale), but its image quality and temporal fidelity scores were above 3.0 (adequate) and artifacts and noise scores were below 3.0 (moderate), suggesting that acceptable diagnostic image quality can be achieved. Additionally, both eightfold accelerated real-time cine and breath-hold cine MRI yielded comparable left ventricular function measurements, with coefficient of variation <10% for left ventricular volumes. Our proposed eightfold accelerated real-time cine MRI with k-t SPARSE-SENSE is a promising modality for rapid imaging of myocardial function. J. Magn. Reson. Imaging 2012;. (c) 2012 Wiley Periodicals, Inc.

PURPOSE: To evaluate the feasibility and perform initial comparative evaluations of a 5-minute comprehensive whole-heart magnetic resonance imaging (MRI) protocol with four image acquisition types: perfusion (PERF), function (CINE), coronary artery imaging (CAI), and late gadolinium enhancement (LGE). MATERIALS AND METHODS: This study protocol was Health Insurance Portability and Accountability Act (HIPAA)-compliant and Institutional Review Board-approved. A 5-minute comprehensive whole-heart MRI examination protocol (Accelerated) using 6-8-fold-accelerated volumetric parallel imaging was incorporated into and compared with a standard 2D clinical routine protocol (Standard). Following informed consent, 20 patients were imaged with both protocols. Datasets were reviewed for image quality using a 5-point Likert scale (0 = non-diagnostic, 4 = excellent) in blinded fashion by two readers. RESULTS: Good image quality with full whole-heart coverage was achieved using the accelerated protocol, particularly for CAI, although significant degradations in quality, as compared with traditional lengthy examinations, were observed for the other image types. Mean total scan time was significantly lower for the Accelerated as compared to Standard protocols (28.99 +/- 4.59 min vs. 1.82 +/- 0.05 min, P < 0.05). Overall image quality for the Standard vs. Accelerated protocol was 3.67 +/- 0.29 vs. 1.5 +/- 0.51 (P < 0.005) for PERF, 3.48 +/- 0.64 vs. 2.6 +/- 0.68 (P < 0.005) for CINE, 2.35 +/- 1.01 vs. 2.48 +/- 0.68 (P = 0.75) for CAI, and 3.67 +/- 0.42 vs. 2.67 +/- 0.84 (P < 0.005) for LGE. Diagnostic image quality for Standard vs. Accelerated protocols was 20/20 (100%) vs. 10/20 (50%) for PERF, 20/20 (100%) vs. 18/20 (90%) for CINE, 18/20 (90%) vs. 18/20 (90%) for CAI, and 20/20 (100%) vs. 18/20 (90%) for LGE. CONCLUSION: This study demonstrates the technical feasibility and promising image quality of 5-minute comprehensive whole-heart cardiac examinations, with simplified scan prescription and high spatial and temporal resolution enabled by highly parallel imaging technology. The study also highlights technical hurdles that remain to be addressed. Although image quality remained diagnostic for most scan types, the reduced image quality of PERF, CINE, and LGE scans in the Accelerated protocol remain a concern. J. Magn. Reson. Imaging 2012. (c) 2012 Wiley Periodicals, Inc.

We examine the problem of estimating the spike trains of multiple neurons from voltage traces recorded on one or more extracellular electrodes. Traditional spike-sorting methods rely on thresholding or clustering of recorded signals to identify spikes. While these methods can detect a large fraction of the spikes from a recording, they generally fail to identify synchronous or near-synchronous spikes: cases in which multiple spikes overlap. Here we investigate the geometry of failures in traditional sorting algorithms, and document the prevalence of such errors in multi-electrode recordings from primate retina. We then develop a method for multi-neuron spike sorting using a model that explicitly accounts for the superposition of spike waveforms. We model the recorded voltage traces as a linear combination of spike waveforms plus a stochastic background component of correlated Gaussian noise. Combining this measurement model with a Bernoulli prior over binary spike trains yields a posterior distribution for spikes given the recorded data. We introduce a greedy algorithm to maximize this posterior that we call "binary pursuit". The algorithm allows modest variability in spike waveforms and recovers spike times with higher precision than the voltage sampling rate. This method substantially corrects cross-correlation artifacts that arise with conventional methods, and substantially outperforms clustering methods on both real and simulated data. Finally, we develop diagnostic tools that can be used to assess errors in spike sorting in the absence of ground truth.

Purpose: To investigate longitudinal changes in global and regional brain volume in patients 1 year after mild traumatic brain injury (MTBI) and to correlate such changes with clinical and neurocognitive metrics. Materials and Methods: This institutional review board-approved study was HIPAA compliant. Twenty-eight patients with MTBI (with 19 followed up at 1 year) with posttraumatic symptoms after injury and 22 matched control subjects (with 12 followed up at 1 year) were enrolled. Automated segmentation of brain regions to compute regional gray matter (GM) and white matter (WM) volumes was performed by using three-dimensional T1-weighted 3.0-T magnetic resonance imaging, and results were correlated with clinical metrics. Pearson and Spearman rank correlation coefficients were computed between longitudinal brain volume and neurocognitive scores, as well as clinical metrics, over the course of the follow-up period. Results: One year after MTBI, there was measurable global brain atrophy, larger than that in control subjects. The anterior cingulate WM bilaterally and the left cingulate gyrus isthmus WM, as well as the right precuneal GM, showed significant decreases in regional volume in patients with MTBI over the 1st year after injury (corrected P < .05); this was confirmed by means of cross-sectional comparison with data in control subjects (corrected P < .05). Left and right rostral anterior cingulum WM volume loss correlated with changes in neurocognitive measures of memory (r = 0.65, P = .005) and attention (r = 0.60, P = .01). At 1-year follow-up, WM volume in the left cingulate gyrus isthmus correlated with clinical scores of anxiety (Spearman rank correlation r = -0.68, P = .007) and postconcussive symptoms (Spearman rank correlation r = -0.65, P = .01). Conclusion: These observations demonstrate structural changes to the brain 1 year after injury after a single concussive episode. Regional brain atrophy is not exclusive to moderate and severe traumatic brain injury but may be seen after mild injury. In particular, the anterior part of the cingulum and the cingulate gyrus isthmus, as well as the precuneal GM, may be distinctively vulnerable 1 year after MTBI. (c) RSNA, 2013.

Sensory signals are transduced at high resolution, but their structure must be stored in a more compact format. Here we provide evidence that the auditory system summarizes the temporal details of sounds using time-averaged statistics. We measured discrimination of 'sound textures' that were characterized by particular statistical properties, as normally result from the superposition of many acoustic features in auditory scenes. When listeners discriminated examples of different textures, performance improved with excerpt duration. In contrast, when listeners discriminated different examples of the same texture, performance declined with duration, a paradoxical result given that the information available for discrimination grows with duration. These results indicate that once these sounds are of moderate length, the brain's representation is limited to time-averaged statistics, which, for different examples of the same texture, converge to the same values with increasing duration. Such statistical representations produce good categorical discrimination, but limit the ability to discern temporal detail.

OBJECTIVE. The purpose of this review is to describe the role of functional renal MRI, or MR renography, in the care of patients with renal masses undergoing partial nephrectomy. CONCLUSION. MR renography can be used to monitor renal functional outcome for patients undergoing partial nephrectomy and may help guide patient selection in this population with elevated risk of chronic kidney disease.

Excessive glucocorticoid exposure during chronic stress causes synapse loss and learning impairment. Under normal physiological conditions, glucocorticoid activity oscillates in synchrony with the circadian rhythm. Whether and how endogenous glucocorticoid oscillations modulate synaptic plasticity and learning is unknown. Here we show that circadian glucocorticoid peaks promote postsynaptic dendritic spine formation in the mouse cortex after motor skill learning, whereas troughs are required for stabilizing newly formed spines that are important for long-term memory retention. Conversely, chronic and excessive exposure to glucocorticoids eliminates learning-associated new spines and disrupts previously acquired memories. Furthermore, we show that glucocorticoids promote rapid spine formation through a non-transcriptional mechanism by means of the LIM kinase-cofilin pathway and increase spine elimination through transcriptional mechanisms involving mineralocorticoid receptor activation. Together, these findings indicate that tightly regulated circadian glucocorticoid oscillations are important for learning-dependent synaptic formation and maintenance. They also delineate a new signaling mechanism underlying these effects.

There is no generally accepted account of the function of the second visual cortical area (V2), partly because no simple response properties robustly distinguish V2 neurons from those in primary visual cortex (V1). We constructed synthetic stimuli replicating the higher-order statistical dependencies found in natural texture images and used them to stimulate macaque V1 and V2 neurons. Most V2 cells responded more vigorously to these textures than to control stimuli lacking naturalistic structure; V1 cells did not. Functional magnetic resonance imaging (fMRI) measurements in humans revealed differences between V1 and V2 that paralleled the neuronal measurements. The ability of human observers to detect naturalistic structure in different types of texture was well predicted by the strength of neuronal and fMRI responses in V2 but not in V1. Together, these results reveal a particular functional role for V2 in the representation of natural image structure.

Sonic Hedgehog (Shh) signals from epithelium to mesenchyme during embryonic lung development, but the roles of Hedgehog (Hh) signaling in postnatal lung development and adult lung are not known. Using Gli1nlacZ reporter mice to identify cells with active Hh signaling, we found that Gli1nlacZ-positive mesenchymal cells are densely and diffusely present up to 2 weeks after birth and decline in number thereafter. In adult mice, Gli1nlacZ-positive cells are present around large airways and vessels and are sparse in alveolar septa. Hh-stimulated cells are mostly fibroblasts; only 10% of Gli1nlacZ-positive cells are smooth muscle cells, and most smooth muscle cells do not have activation of Hh signaling. After bleomycin injury there are abundant Gli1nlacZ-positive mesenchymal cells in fibrotic lesions and increased numbers of Gli1nlacZ-positive cells in preserved alveolar septa. Inhibition of Hh signaling with an antibody against all Hedgehog isoforms does not reduce bleomycin-induced fibrosis, but adenovirus-mediated over-expression of Shh increases collagen production in this model. Inhibition of Hh signaling during early postnatal lung development causes airspace enlargement without diminished alveolar septation. Reduction of Hh signaling in the later stages of postnatal lung development may be required for normal thinning and maturation of alveolar septa.