Faculty Bibliography

OBJECTIVE: The purpose of this article was to assess the feasibility of golden-angle radial acquisition with compress sensing reconstruction (Golden-angle RAdial Sparse Parallel [GRASP]) for acquiring high temporal resolution data for pharmacokinetic modeling while maintaining high image quality in patients with Crohn disease terminal ileitis. MATERIALS AND METHODS: Fourteen patients with biopsy-proven Crohn terminal ileitis were scanned using both contrast-enhanced GRASP and Cartesian breath-hold (volume-interpolated breath-hold examination [VIBE]) acquisitions. GRASP data were reconstructed with 2.4-second temporal resolution and fitted to the generalized kinetic model using an individualized arterial input function to derive the volume transfer coefficient (K(trans)) and interstitial volume (ve). Reconstructions, including data from the entire GRASP acquisition and Cartesian VIBE acquisitions, were rated for image quality, artifact, and detection of typical Crohn ileitis features. RESULTS: Inflamed loops of ileum had significantly higher K(trans) (3.36 +/- 2.49 vs 0.86 +/- 0.49 min(-1), p < 0.005) and ve (0.53 +/- 0.15 vs 0.20 +/- 0.11, p < 0.005) compared with normal bowel loops. There were no significant differences between GRASP and Cartesian VIBE for overall image quality (p = 0.180) or detection of Crohn ileitis features, although streak artifact was worse with the GRASP acquisition (p = 0.001). CONCLUSION: High temporal resolution data for pharmacokinetic modeling and high spatial resolution data for morphologic image analysis can be achieved in the same acquisition using GRASP.

PURPOSE: We used a combined intravoxel incoherent motion-diffusion tensor imaging (IVIM-DTI) methodology to distinguish structural from flow effects on renal diffusion anisotropy. METHODS: Eight volunteers were examined with IVIM-DTI at 3T with 20 diffusion directions and 10 b-values. Mean diffusivity (MD) and fractional anisotropy (FA) from DTI analysis were calculated for low (b 200 s/mm2 ), and full b-value ranges. IVIM-parameters perfusion-fraction fP , pseudo-diffusivity Dp , and tissue-diffusivity Dt were first calculated independently on a voxelwise basis for all directions. After estimating a fixed isotropic fp from these data, global anisotropies of Dt and Dp in the cortex and medulla were determined in a constrained cylindrical description and visualized using polar plots and cosine scatterplots. RESULTS: For all b-value ranges, medullary FA was significantly higher than that of the cortex. The corticomedullary difference was smaller for the high b-value range. Significantly higher fp and Dt were determined for the cortex and showed a significantly higher directional variance in the medulla. Polar plot analysis displayed nearly isotropic Dp and Dt in the cortex and anisotropy in the medulla. CONCLUSION: Both flow and microstructure apparently contribute to the medullary diffusion anisotropy. The described novel method may be useful in separating decreased tubular flow from irreversible structural tubular damage, for example, in diabetic nephropathy or during allograft rejection. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc.

OBJECT Automated eye movement tracking may provide clues to nervous system function at many levels. Spatial calibration of the eye tracking device requires the subject to have relatively intact ocular motility that implies function of cranial nerves (CNs) III (oculomotor), IV (trochlear), and VI (abducent) and their associated nuclei, along with the multiple regions of the brain imparting cognition and volition. The authors have developed a technique for eye tracking that uses temporal rather than spatial calibration, enabling detection of impaired ability to move the pupil relative to normal (neurologically healthy) control volunteers. This work was performed to demonstrate that this technique may detect CN palsies related to brain compression and to provide insight into how the technique may be of value for evaluating neuropathological conditions associated with CN palsy, such as hydrocephalus or acute mass effect. METHODS The authors recorded subjects' eye movements by using an Eyelink 1000 eye tracker sampling at 500 Hz over 200 seconds while the subject viewed a music video playing inside an aperture on a computer monitor. The aperture moved in a rectangular pattern over a fixed time period. This technique was used to assess ocular motility in 157 neurologically healthy control subjects and 12 patients with either clinical CN III or VI palsy confirmed by neuro-ophthalmological examination, or surgically treatable pathological conditions potentially impacting these nerves. The authors compared the ratio of vertical to horizontal eye movement (height/width defined as aspect ratio) in normal and test subjects. RESULTS In 157 normal controls, the aspect ratio (height/width) for the left eye had a mean value +/- SD of 1.0117 +/- 0.0706. For the right eye, the aspect ratio had a mean of 1.0077 +/- 0.0679 in these 157 subjects. There was no difference between sexes or ages. A patient with known CN VI palsy had a significantly increased aspect ratio (1.39), whereas 2 patients with known CN III palsy had significantly decreased ratios of 0.19 and 0.06, respectively. Three patients with surgically treatable pathological conditions impacting CN VI, such as infratentorial mass effect or hydrocephalus, had significantly increased ratios (1.84, 1.44, and 1.34, respectively) relative to normal controls, and 6 patients with supratentorial mass effect had significantly decreased ratios (0.27, 0.53, 0.62, 0.45, 0.49, and 0.41, respectively). These alterations in eye tracking all reverted to normal ranges after surgical treatment of underlying pathological conditions in these 9 neurosurgical cases. CONCLUSIONS This proof of concept series of cases suggests that the use of eye tracking to detect CN palsy while the patient watches television or its equivalent represents a new capacity for this technology. It may provide a new tool for the assessment of multiple CNS functions that can potentially be useful in the assessment of awake patients with elevated intracranial pressure from hydrocephalus or trauma.

PURPOSE: To retrospectively assess the utility of whole-lesion apparent diffusion coefficient (ADC) metrics in characterizing the Gleason 4 component of Gleason 7 prostate cancer (PCa) at radical prostatectomy. MATERIALS AND METHODS: Seventy patients underwent phased-array coil 3T-magnetic resonance imaging (MRI) before prostatectomy. A uropathologist mapped locations and Gleason 4 percentage (G4%) of Gleason 7 tumors. Two radiologists independently reviewed ADC maps, aware of tumor locations but not G4%, and placed a volume-of-interest (VOI) on all slices including each lesion on the ADC map to obtain whole-lesion mean ADC and ADC entropy. Entropy reflects textural variation and increases with greater macroscopic heterogeneity. Performance for characterizing Gleason 7 tumors was assessed with mixed-model analysis of variance (ANOVA) and logistic regression. RESULTS: Among 84 Gleason 7 tumors (G4% 5%-85%, median 30%; 59 Gleason 3+4, 25 Gleason 4+3), ADC entropy was significantly higher in Gleason 4+3 than Gleason 3+4 tumors (R1: 5.27 +/- 0.61 vs. 4.62 +/- 0.78, P = 0.001; R2: 5.91 +/- 0.32 vs. 5.57 +/- 0.56, P = 0.004); mean ADC was not significantly different between these groups (R1: 0.90 +/- 0.15*10-3 cm2 /s vs. 0.98 +/- 0.21*10-3 cm2 /s, P = 0.075; R2: 1.06 +/- 0.19*10-3 cm2 /s vs. 1.14 +/- 0.16*10-3 cm2 /s, P = 0.083). The area under the receiver operating characteristic (ROC) curve (AUC) for differentiating groups was significantly higher with ADC entropy than mean ADC for one observer (R1: 0.74 vs. 0.57, P = 0.027; R2: 0.69 vs. 0.61, P = 0.329). For R1, correlation with G4% was moderate for ADC entropy (r = 0.45) and weak for mean ADC (r = -0.25). For R2, correlation with G4% was moderate for ADC entropy (r = 0.41) and mean ADC (r = -0.32). For both readers, ADC entropy (P = 0.028-0.003), but not mean ADC (P = 0.384-0.854), was a significant independent predictor of G4%. CONCLUSION: Whole-lesion ADC entropy outperformed mean ADC in characterizing Gleason 7 tumors and may help refine prognosis for this heterogeneous PCa subset. J. Magn. Reson. Imaging 2014. (c) 2014 Wiley Periodicals, Inc.

Purpose: To determine if brain atrophy can be calculated by performing volumetric analysis on conventional computed tomography (CT) scans in spite of relatively low contrast for this modality.Materials & Method: CTs for 73 patients from the local Veteran Affairs database were selected. Exclusion criteria: AD, NPH, tumor, and alcohol abuse. Protocol: conventional clinical acquisition (Toshiba; helical, 120 kVp, X-ray tube current 300mA, slice thickness 3-5mm). Locally developed, automatic algorithm was used to segment intracranial cavity (ICC) using (a) white matter seed (b) constrained growth, limited by inner skull layer and (c) topological connectivity. ICC was further segmented into CSF and brain parenchyma using a threshold of 16 Hu. Results: Age distribution: 25-95yrs; (Mean 67+or-17.5yrs.). Significant correlation was found between age and CSF/ICC(r=0.695, p<0.01 2-tailed). A quadratic model (y=0.06-0.001x+2.56x10 -5x 2 ; where y=CSF/ICC and x=age) was a better fit to data (r=0.716, p < 0.01). This is in agreement with MRI literature. For example, Smith et al. found annual CSF/ICC increase in 58 - 94.5 y.o. individuals to be 0.2%/year, whereas our data, restricted to the same age group yield 0.3%/year(0.2-0.4%/yrs. 95%C.I.). Slightly increased atrophy among elderly VA patients is attributable to the presence of other comorbidities. Conclusion: Brain atrophy can be reliably calculated using automated software and conventional CT. Compared to MRI, CT is more widely available, cheaper, and less affected by head motion due to ~100 times shorter scan time. Work is in progress to improve the precision of the measurements, possibly leading to assessment of longitudinal changes within the patient

INTRODUCTION: Neurofibrillary tau pathology and amyloid beta (Abeta) plaques, characteristic lesions of Alzheimer's disease (AD), show different neocortical laminar distributions. NFT-tau pathology tends to be located closer to the gray-white-matter boundary (G-WB) whereas Abeta is dispersed throughout the width of the cortical ribbon. METHODS: Using PET radiotracers for tau and Abeta lesions, we developed an image analysis tool to measure the distance of tracer-positive voxels to the G-WB. We studied 5 AD and 5 healthy subjects with both 18F-THK5117 (tau) and 11C-PiB (Abeta) PET. RESULTS: We observed that on average tau positive-voxels were closer to the white matter than the Abeta positive voxels. This effect was found for all AD subjects and for all regions, both before and after regionally adjusting for the non-specific white matter binding of both tracers. The differential laminar pattern was validated at post mortem. CONCLUSION: Within cortical lamina distance measures may be of value in testing PET tracers for their anatomical selectivity.

PURPOSE: The purpose of this study was to estimate perfusion metrics in healthy and cirrhotic liver with pharmacokinetic modeling of high-temporal resolution reconstruction of continuously acquired free-breathing gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced acquisition in patients undergoing clinically indicated liver magnetic resonance imaging. SUBJECTS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant prospective study, 9 cirrhotic and 10 noncirrhotic patients underwent clinical magnetic resonance imaging, which included continuously acquired radial stack-of-stars 3-dimensional gradient recalled echo sequence with golden-angle ordering scheme in free breathing during contrast injection. A total of 1904 radial spokes were acquired continuously in 318 to 340 seconds. High-temporal resolution data sets were formed by grouping 13 spokes per frame for temporal resolution of 2.2 to 2.4 seconds, which were reconstructed using the golden-angle radial sparse parallel technique that combines compressed sensing and parallel imaging. High-temporal resolution reconstructions were evaluated by a board-certified radiologist to generate gadolinium concentration-time curves in the aorta (arterial input function), portal vein (venous input function), and liver, which were fitted to dual-input dual-compartment model to estimate liver perfusion metrics that were compared between cirrhotic and noncirrhotic livers. RESULTS: The cirrhotic livers had significantly lower total plasma flow (70.1 +/- 10.1 versus 103.1 +/- 24.3 mL/min per 100 mL; P < 0.05), lower portal venous flow (33.4 +/- 17.7 versus 89.9 +/- 20.8 mL/min per 100 mL; P < 0.05), and higher arterial perfusion fraction (52.0% +/- 23.4% versus 12.4% +/- 7.1%; P < 0.05). The mean transit time was higher in the cirrhotic livers (24.4 +/- 4.7 versus 15.7 +/- 3.4 seconds; P < 0.05), and the hepatocellular uptake rate was lower (3.03 +/- 2.1 versus 6.53 +/- 2.4 100/min; P < 0.05). CONCLUSIONS: Liver perfusion metrics can be estimated from free-breathing dynamic acquisition performed for every clinical examination without additional contrast injection or time. This is a novel paradigm for dynamic liver imaging.

PURPOSE: To explore associations of whole-lesion histogram diffusion metrics with pathologic findings and subsequent metastatic disease in bladder cancer patients undergoing radical cystectomy. METHODS: Twenty-three bladder cancer patients (21M, 2F; mean 70 +/- 11 years) underwent MRI before cystectomy. A volume-of-interest was placed on all slices on the ADC map encompassing each lesion. Whole-lesion mean, kurtosis, and skewness of ADC were calculated and compared with T stage and pelvic nodal status at cystectomy and with subsequent metastasis in 20/25 patients with available follow-up. RESULTS: At cystectomy, 39 % (9/23) were stage T2, 61 % (14/23) >/=T3, and 28 % (5/23) exhibited positive nodes; 35 % (7/20) developed later metastases. Mean ADC was significantly lower in stage >/=T3 than in lower stage tumors (1.20 +/- 0.36 x 10-3 vs. 1.55 +/- 0.36 x 10-3 mm2/s; p = 0.044), but showed no association with nodal or metastatic disease (p = 0.362-0.709). Kurtosis was significantly lower in tumors with, compared to without, nodal disease (-0.05 +/- 0.29 vs. 0.91 +/- 1.16; p = 0.037), and showed a non-significant decrease in tumors with, compared to without, later metastases (0.23 +/- 0.63 vs. 0.83 +/- 0.89; p = 0.088). Kurtosis was not associated with T stage (p = 0.811), and skew was not associated with any outcome (p = 0.516-0.643). Mean ADC achieved highest AUC for identification of stage >/=T3 (AUC = 0.754 vs. 0.516-0.643 for other metrics). Kurtosis achieved highest AUC for nodal disease (AUC = 0.811 vs. 0.522-0.556 for other metrics) and metastases (AUC = 0.736 vs. 0.516-0.626 for other metrics). Only difference in AUC between skewness and kurtosis for nodal disease was significant (p = 0.031). CONCLUSION: While requiring larger studies, kurtosis has potential to complement mean ADC in bladder cancer prognosis using whole-lesion histogram analysis.

The accumulation of amyloid-beta (Abeta) plaques is a central feature of Alzheimer's disease (AD). First reported in animal models, it remains uncertain if peripheral inflammatory and/or infectious conditions in humans can promote Abeta brain accumulation. Periodontal disease, a common chronic infection, has been previously reported to be associated with AD. Thirty-eight cognitively normal, healthy, and community-residing elderly (mean age, 61 and 68% female) were examined in an Alzheimer's Disease Research Center and a University-Based Dental School. Linear regression models (adjusted for age, apolipoprotein E, and smoking) were used to test the hypothesis that periodontal disease assessed by clinical attachment loss was associated with brain Abeta load using 11C-Pittsburgh compound B (PIB) positron emission tomography imaging. After adjusting for confounders, clinical attachment loss (>/=3 mm), representing a history of periodontal inflammatory/infectious burden, was associated with increased PIB uptake in Abeta vulnerable brain regions (p = 0.002). We show for the first time in humans an association between periodontal disease and brain Abeta load. These data are consistent with the previous animal studies showing that peripheral inflammation/infections are sufficient to produce brain Abeta accumulations.

PURPOSE: One of the interesting features of the amyloid tracer Pittsburgh compound B (PiB) is that it generates a signal in the white matter (WM) in both healthy subjects and cognitively impaired individuals. This characteristic gave rise to the possibility that PiB could be used to trace WM pathology. In a group of cognitively healthy elderly we examined PiB retention in normal-appearing WM (NAWM) and WM lesions (WML), one of the most common brain pathologies in aging. METHODS: We segmented WML and NAWM on fluid attenuation inversion recovery (FLAIR) images of 73 subjects (age 61.9 +/- 10.0, 71 % women). PiB PET images were corrected for partial volume effects and coregistered to FLAIR images and WM masks. WML and NAWM PiB signals were then extracted. RESULTS: PiB retention in WML was lower than in NAWM (p < 0.001, 14.6 % reduction). This was true both for periventricular WML (p < 0.001, 17.8 % reduction) and deep WML (p = 0.001, 7.5 % reduction). CONCLUSION: PiB binding in WM is influenced by the presence of WML, which lower the signal. Our findings add to the growing evidence that PiB can depict WM pathology and should prompt further investigations into PiB binding targets in WM.