High-resolution magnetic resonance imaging-based atlases for the young and adolescent domesticated pig (Sus scrofa).

BACKGROUND: Neurodevelopmental studies utilize the pig as a translational animal model due to anatomical and morphological similarities between the pig and human brain. However, neuroimaging resources are not as well developed for the pig as they are for humans and other animal models. We established a magnetic resonance imaging-based brain atlas at two different ages for biomedical studies utilizing the pig as a preclinical model. NEW METHOD: Twenty artificially-reared domesticated male pigs (Sus scrofa) and thirteen sow-reared adolescent domesticated male pigs (Sus scrofa) underwent a series of scans measuring brain macrostructure, microstructure, and arterial cerebral blood volume. RESULTS: An atlas for the 4-week-old and 12-week-old pig were created along with twenty-six regions of interest. Normative data for brain measures were obtained and detailed descriptions of the data processing pipelines were provided. COMPARISON WITH EXISTING METHOD: Atlases at the two different ages were created for the pig utilizing newer imaging technology and software. This facilitates the performance of longitudinal studies and enables more precise volume measurements in pigs of various ages by appropriately representing the neuroanatomical features of younger and older pigs and accommodating the proportion differences of the brain over time. CONCLUSION: Two high-resolution MRI brain atlases specific to the domesticated young and adolescent pig were created using defined image acquisition and data processing methods to facilitate the generation of high-quality normative data for neurodevelopmental research.

Decreased resting perfusion in precuneus and posterior cingulate cortex predicts tinnitus severity.

Functional magnetic resonance imaging has been increasingly used to understand the mechanisms involved in subjective tinnitus; however, researchers have struggled to reach a consensus about a primary mechanistic model to explain tinnitus. While many studies have used functional connectivity of the BOLD signal to understand how patterns of activity change with tinnitus severity, there is much less research on whether there are differences in more fundamental physiology, including cerebral blood flow, which may help inform the BOLD measures. Here, arterial spin labeling was used to measure perfusion in four regions-of-interest, guided by current models of tinnitus, in a sample of 60 tinnitus patients and 31 control subjects. We found global reductions in cerebral perfusion in tinnitus compared with controls. Additionally, we observed a significant negative correlation between tinnitus severity and perfusion. These results demonstrate that examining perfusion from the whole brain may present a complementary tool for studying tinnitus. More research will help better understand the physiology underlying these differences in perfusion.

Dissociating tinnitus patients from healthy controls using resting-state cyclicity analysis and clustering.

Chronic tinnitus is a common and sometimes debilitating condition that lacks scientific consensus on physiological models of how the condition arises as well as any known cure. In this study, we applied a novel cyclicity analysis, which studies patterns of leader-follower relationships between two signals, to resting-state functional magnetic resonance imaging (rs-fMRI) data of brain regions acquired from subjects with and without tinnitus. Using the output from the cyclicity analysis, we were able to differentiate between these two groups with 58-67% accuracy by using a partial least squares discriminant analysis. Stability testing yielded a 70% classification accuracy for identifying individual subjects' data across sessions 1 week apart. Additional analysis revealed that the pairs of brain regions that contributed most to the dissociation between tinnitus and controls were those connected to the amygdala. In the controls, there were consistent temporal patterns across frontal, parietal, and limbic regions and amygdalar activity, whereas in tinnitus subjects, this pattern was much more variable. Our findings demonstrate a proof-of-principle for the use of cyclicity analysis of rs-fMRI data to better understand functional brain connectivity and to use it as a tool for the differentiation of patients and controls who may differ on specific traits.

Comparing Cyclicity Analysis With Pre-established Functional Connectivity Methods to Identify Individuals and Subject Groups Using Resting State fMRI.

The resting state fMRI time series appears to have cyclic patterns, which indicates presence of cyclic interactions between different brain regions. Such interactions are not easily captured by pre-established resting state functional connectivity methods including zero-lag correlation, lagged correlation, and dynamic time warping distance. These methods formulate the functional interaction between different brain regions as similar temporal patterns within the time series. To use information related to temporal ordering, cyclicity analysis has been introduced to capture pairwise interactions between multiple time series. In this study, we compared the efficacy of cyclicity analysis with aforementioned similarity-based techniques in representing individual-level and group-level information. Additionally, we investigated how filtering and global signal regression interacted with these techniques. We obtained and analyzed fMRI data from patients with tinnitus and neurotypical controls at two different days, a week apart. For both patient and control groups, we found that the features generated by cyclicity and correlation (zero-lag and lagged) analyses were more reliable than the features generated by dynamic time warping distance in identifying individuals across visits. The reliability of all features, except those generated by dynamic time warping, improved as the global signal was regressed. Nevertheless, removing fluctuations >0.1 Hz deteriorated the reliability of all features. These observations underscore the importance of choosing appropriate preprocessing steps while evaluating different analytical methods in describing resting state functional interactivity. Further, using different machine learning techniques including support vector machines, discriminant analyses, and convolutional neural networks, our results revealed that the manifestation of the group-level information within all features was not sufficient enough to dissociate tinnitus patients from controls with high sensitivity and specificity. This necessitates further investigation regarding the representation of group-level information within different features to better identify tinnitus-related alternation in the functional organization of the brain. Our study adds to the growing body of research on developing diagnostic tools to identify neurological disorders, such as tinnitus, using resting state fMRI data.

Noninvasive imaging of cerebral blood volume in piglets with vascular occupancy MR imaging and inflow vascular space occupancy with dynamic subtraction.

Accurate quantitative non-invasive assessments of arterial cerebral blood volume (aCBV) can greatly benefit the study of cerebral vascular health in both humans and in animal models. In recent years, progress has been made in the techniques available to quantify CBV with magnetic resonance imaging (MRI). Here, we compared a non-invasive technique, measuring inflowing vascular space occupancy with dynamic subtraction (iVASO-ds) with a contrast-based vascular space occupancy measurement in piglets. In addition, we measured how the iVASO-ds derived aCBV changed with piglet development from 4 weeks to 8 weeks. Our results indicate that there is a significant correlation between the non-invasive iVASO-ds derived aCBV and CBV quantified using a gadolinium contrast agent, despite the contrast-based method providing significantly higher estimates of CBV resulting from challenges inherent to using the contrast-based technique. In addition, it was possible to see significant increases in blood volume across 4 weeks to 8 weeks in pig development with the non-invasive technique. Our results suggest that the non-invasive technique, iVASO-ds can assess aCBV in the developing piglet, both cross-sectionally and longitudinally, and has significant advantages over the contrast-based quantification method.