Faculty Bibliography

Background: A great deal of current research is aiming to better understand what happens to brains affected by Alzheimer's disease, both structurally and metabolically. However, little is known about how the brain ages in the cognitively normal adult population. There is also a limited understanding as to how glucose metabolism and brain atrophy interact in the normal human brain. To our knowledge, this study is the first to longitudinally analyze measures of atrophy and metabolism in both MRI and FDG-PET in cognitively normal subjects. Methods: 45 cognitively normal subjects were studied longitudinally over a span of at least 1.5 years (average = 5.99 years). Each had at least two structural MRIs and 2 FDG-PET scans. Free Surfer was used to analyze ventricle and intracranial volume. This was turned into an intracranial volume ratio to get a normalized picture of brain atrophy. A hippocampal masking technique (HipMask) was used to analyze the FDG-PET scans for changes in metabolic rates in regions normally affected by Alzheimer's disease (precuneus/posterior cingulate, hippocampus, inferior parietal lobe), as well as regions affected by normal aging (prefrontal cortex and cerebellum). Results: Mixed model analysis indicates that ventricle enlargement occurs in the cognitively normal adult brain as early as adult middle age (t = 7.050, p < .001), with a particular acceleration after the age of 65 (t = 2.878, p = .004). However, the mixed model results did not show any evidence of a concomitant decrease in rate with age, nor any acceleration, in regional metabolism after controlling for brain atrophy. Conclusions: Our results show that brain atrophy increases over the adult lifespan. These changes appear to accelerate over time. However, metabolically, we did not find any significant results with regard to change over time. This is in contrast to Alzheimer's disease, where literature has shown metabolic decreases in frontal and parietal regions, particularly in precuneus/posterior cingulate. Our !

AIM: To assess a novel method of three-dimensional (3D) co-registration of prostate cancer digital histology and in-vivo multiparametric magnetic resonance imaging (mpMRI) image sets for clinical usefulness. MATERIAL AND METHODS: A software platform was developed to achieve 3D co-registration. This software was prospectively applied to three patients who underwent radical prostatectomy. Data comprised in-vivo mpMRI [T2-weighted, dynamic contrast-enhanced weighted images (DCE); apparent diffusion coefficient (ADC)], ex-vivo T2-weighted imaging, 3D-rebuilt pathological specimen, and digital histology. Internal landmarks from zonal anatomy served as reference points for assessing co-registration accuracy and precision. RESULTS: Applying a method of deformable transformation based on 22 internal landmarks, a 1.6 mm accuracy was reached to align T2-weighted images and the 3D-rebuilt pathological specimen, an improvement over rigid transformation of 32% (p = 0.003). The 22 zonal anatomy landmarks were more accurately mapped using deformable transformation than rigid transformation (p = 0.0008). An automatic method based on mutual information, enabled automation of the process and to include perfusion and diffusion MRI images. Evaluation of co-registration accuracy using the volume overlap index (Dice index) met clinically relevant requirements, ranging from 0.81-0.96 for sequences tested. Ex-vivo images of the specimen did not significantly improve co-registration accuracy. CONCLUSION: This preliminary analysis suggests that deformable transformation based on zonal anatomy landmarks is accurate in the co-registration of mpMRI and histology. Including diffusion and perfusion sequences in the same 3D space as histology is essential further clinical information. The ability to localize cancer in 3D space may improve targeting for image-guided biopsy, focal therapy, and disease quantification in surveillance protocols.

OBJECTIVE. The objective of our study was to report our initial experience with dynamic contrast-enhanced MRI (DCE-MRI) for perfusion quantification of hepatocellular carcinoma (HCC) and surrounding liver. SUBJECTS AND METHODS. DCE-MRI of the liver was prospectively performed on 31 patients with HCC (male-female ratio, 26:5; mean age, 61 years; age range, 41-83 years). A dynamic coronal 3D FLASH sequence was performed at 1.5 T before and after injection of gadolinium-based contrast agent with an average temporal resolution of 3.8 seconds. Regions of interest were drawn on the abdominal aorta, portal vein, liver parenchyma, and HCC lesions by two observers in consensus. Time-activity curves were analyzed using a dual-input single-compartment model. The following perfusion parameters were obtained: arterial flow, portal venous flow, arterial fraction, distribution volume, and mean transit time (MTT). RESULTS. Thirty-three HCCs (mean size, 3.9 cm; range, 1.1-12.6 cm) were evaluated in 26 patients. When compared with liver parenchyma, HCC showed significantly higher arterial hepatic blood flow and arterial fraction (p < 0.0001) and significantly lower distribution volume and portal venous hepatic blood flow (p < 0.0001-0.023), with no difference in MTT. Untreated HCCs (n = 16) had a higher arterial fraction and lower portal venous hepatic blood flow value than chemoembolized HCCs (n = 17, p < 0.04). CONCLUSION. DCE-MRI can be used to quantify perfusion metrics of HCC and liver parenchyma and to assess perfusion changes after HCC chemoembolization.

Purpose: To assess whether automated texture analysis of CT images enables discrimination among pathologic classes of lung adenocarcinomas, and thus serves as an in vivo biomarker of lung cancer prognosis. Materials and Methods: Chest CTs of 30 nodules in 30 patients with resected adenocarcinomas were evaluated by a pulmonary pathologist who classified each resected cancer according to the International Association for the Study of Lung Cancer (IASLC) system. The categories included adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), lepidic-predominant adenocarcinoma (LPA), and other invasive adenocarcinomas (INV). 3D volumes of interest (VOIs) and 2D regions of interest (ROIs) were then constructed for each nodule. A comprehensive set of N=279 texture parameters were computed for both 3D and 2D regions. Clustering and classification of these parameters were performed with linear discriminant analysis (LDA) using features determined by optimal subsets. Results: Of the 30 adenocarcinomas, there were 13 INV, 11 LPA, 3 MIA, and 3 AIS. AIS and MIA groups were analyzed together. With all 3 classes, LDA classified 17 of 30 nodules correctly using the nearest neighbor (k=1) method. When only the two largest classes (INV and LPA) were used, 21 of 24 nodules were classified correctly. With 3 classes and 2D texture analysis, and when using only the two largest groups, LDA was able to correctly classify all nodules. Conclusion: CT texture parameters determined by optimal subsets allows for effective clustering of adenocarcinoma classes. These results suggest the potential use of automated (or computer-assisted) CT image analysis to predict the invasive pathologic character of lung nodules. Our approach overcomes the limitations of current radiologic interpretation, such as subjectivity, interand intra-observer variability, and the effect of reader experience

Object In patients with tuberous sclerosis complex (TSC), the tuber-to-brain proportion (TBP) is a marker of seizure severity and cognitive function. However, few studies have quantified the TBP. Furthermore, authors of these studies have measured the TBP at only a single time point, despite the fact that tuber cells were found to express proliferation markers, suggesting that they may be dynamic lesions. Authors of the present study used a semi-automated tuber segmentation program to determine whether the TBP changes over time. Methods Axial FLAIR MR images were retrospectively identified for patients with TSC who had undergone imaging at the authors' institution between February 1998 and June 2009. Using FireVoxel software, the TBP was measured for each patient at a minimum interval of 2 years. Results Twelve patients meeting the study inclusion criteria were identified. The mean TBP was 1.88% (range 0.38%-3.70%). Eight patients demonstrated minimal changes and 3 patients demonstrated small increases in TBP. The remaining patient exhibited a decrease of 1.00%, which correlated with a visible decrease in the size of 2 cerebellar lesions. Conclusions Semi-automated brain segmentation is a valuable tool in the longitudinal study of tubers. A subset of patients with TSC, particularly those with cerebellar lesions, may exhibit changes in the TBP over time.

There is growing evidence that cerebrovascular reactivity to carbon dioxide (CVRCO2) is impaired in Alzheimer's disease (AD). Preclinical and animal studies suggest chronic hypercontractility in brain vessels in AD. We review (a) preclinical studies of mechanisms for impaired CVRCO2 in AD; (b) clinical studies of cerebrovascular function in subjects with AD dementia, mild cognitive impairment (MCI), and normal cognition. Although results of clinical studies are inconclusive, an increasing number of reports reveal an impairment of vascular reactivity to carbon dioxide in subjects with AD, and possibly also in MCI. Thus, CVRCO2 may be an attractive means to detect an early vascular dysfunction in subjects at risk.

OBJECTIVES: The aim of this study was to assess the impact of oral water and intravenous furosemide challenges on blood oxygenation level-dependent magnetic resonance imaging measurements in the kidney and to examine the contribution of R2 (=1/T2) to changes in R2* (=1/T2*). MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act-compliant study had institutional review board approval, and written informed consent was obtained from all subjects. Nine healthy volunteers were imaged at 3 T on 2 visits. During each visit, a baseline fasting magnetic resonance acquisition was followed by a diuretic challenge: oral water load for the first visit and furosemide for the second. R2* and R2 values in the renal cortex and medulla were measured using multiple gradient echo and multiple spin echo sequences, respectively, and R2' values were computed as R2' = R2* - R2. Timed urinary output was also measured. RESULTS: Averaged across all subjects, the R2* response to furosemide was greater than to water and greater in the medulla than the cortex. The mean R2 responses exhibited the same trends but were uniformly smaller than the mean R2* responses. The peak changes in R2* and R2 appeared, on average, 10 to 14 minutes before peak urinary output. The median percentage contribution of R2 to R2* changes was 16% in the medulla after both challenges. In the cortex, the median contribution was 48% after water load and 58% after furosemide challenge. CONCLUSIONS: The contributions of R2 to R2* changes after water load and furosemide challenge are not negligible, especially in the renal cortex. In routine clinical practice, R2* could be used alone as a rough surrogate for R2' in the medulla. However, in the cortex, both R2 and R2* should be measured to obtain accurate values of R2'.

To test the hypotheses that global decreased neuro-axonal integrity reflected by decreased N-acetylaspartate (NAA) and increased glial activation reflected by an elevation in its marker, the myo-inositol (mI), present in a CD8-depleted rhesus macaque model of HIV-associated neurocognitive disorders. To this end, we performed quantitative MRI and 16 x 16 x 4 multivoxel proton MRS imaging (TE/TR = 33/1400 ms) in five macaques pre- and 4-6 weeks post-simian immunodeficiency virus infection. Absolute NAA, creatine, choline (Cho), and mI concentrations, gray and white matter (GM and WM) and cerebrospinal fluid fractions were obtained. Global GM and WM concentrations were estimated from 224 voxels (at 0.125 cm(3) spatial resolution over ~35% of the brain) using linear regression. Pre- to post-infection global WM NAA declined 8%: 6.6 +/- 0.4 to 6.0 +/- 0.5 mM (p = 0.05); GM Cho declined 20%: 1.3 +/- 0.2 to 1.0 +/- 0.1 mM (p < 0.003); global mI increased 11%: 5.7 +/- 0.4 to 6.5 +/- 0.5 mM (p < 0.03). Global GM and WM brain volume fraction changes were statistically insignificant. These metabolic changes are consistent with global WM (axonal) injury and glial activation, and suggest a possible GM host immune response

PURPOSE: To assess two methods of fat and fibroglandular tissue (FGT) segmentation for measuring breast MRI FGT volume and FGT%, the volume percentage of FGT in the breast, in longitudinal studies. MATERIALS AND METHODS: Nine premenopausal women provided one MRI per week for 4 weeks during a natural menstrual cycle for a total of 36 datasets. We compared a fuzzy c-means (FC) and a 3-point Dixon segmentation method for estimation of changes in FGT volume and FGT% across the menstrual cycle. We also assessed whether differences due to changes in positioning each week could be minimized by coregistration, i.e., the application of the breast boundary selected at one visit to images obtained at other visits. RESULTS: FC and Dixon FGT volume were highly correlated (r = 0.93, P < 0.001), as was FC and Dixon FGT% (r = 0.86, P = 0.01), although Dixon measurements were on average 10-20% higher. Although FGT measured by both methods showed the expected pattern of increase during the menstrual cycle, the magnitude, and for one woman the direction, of change varied according to the method used. Measurements of FGT for coregistered images were in close agreement with those for which the boundaries were determined independently. CONCLUSION: The method of segmentation of fat and FGT tissue may have an impact on the results of longitudinal studies of changes in breast MRI FGT. J. Magn. Reson. Imaging 2012;. (c) 2012 Wiley Periodicals, Inc.