[Show abstract][Hide abstract] ABSTRACT: Background:
Neuroimaging studies in younger adults have demonstrated sex differences in brain processing of painful experimental stimuli. Such differences may contribute to findings that women suffer disproportionately from pain. It is not known whether sex-related differences in pain processing extend to older adults.
This cross-sectional study investigated sex differences in pain reports and brain response to pain in 12 cognitively healthy older female adults and 12 cognitively healthy age-matched older male adults (age range 65-81, median = 67). Participants underwent psychophysical assessments of thermal pain responses, functional MRI, and psychosocial assessment.
When compared to older males, older females reported experiencing mild and moderate pain at lower stimulus intensities (i.e., exhibited greater pain sensitivity; Cohen's d = 0.92 and 0.99, respectively, p < 0.01) yet did not report greater pain-associated unpleasantness. Imaging results indicated that, despite the lower stimulus intensities required to elicit mild pain detection in females, they exhibited less deactivations than males in regions associated with the default mode network (DMN) and in regions associated with pain affect (bilateral dorsolateral prefrontal cortex, somatomotor area, rostral anterior cingulate cortex (rACC), and dorsal ACC). Conversely, at moderate pain detection levels, males exhibited greater activation than females in several ipsilateral regions typically associated with pain sensation (e.g., primary (SI) and secondary somatosensory cortices (SII) and posterior insula). Sex differences were found in the association of brain activation in the left rACC with pain unpleasantness. In the combined sample of males and females, brain activation in the right secondary somatosensory cortex was associated with pain unpleasantness.
Cognitively healthy older adults in the sixth and seventh decades of life exhibit similar sex differences in pain sensitivity compared to those reported in younger individuals. However, older females did not find pain to be more unpleasant. Notably, increased sensitivity to mild pain in older females was reflected via less brain deactivation in regions associated with both the DMN and in pain affect. Current findings elevate the rACC as a key region associated with sex differences in reports of pain unpleasantness and brain deactivation in older adults. Also, pain affect may be encoded in SII in both older males and females.
Biology of Sex Differences 11/2015; 6(1):25. DOI:10.1186/s13293-015-0041-y · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Functional magnetic resonance imaging usually detects changes in blood oxygenation level dependent (BOLD) signals from T2*-sensitive acquisitions, and is most effective in detecting activity in brain cortex which is irrigated by rich vasculature to meet high metabolic demands. We recently demonstrated that MRI signals from T2*-sensitive acquisitions in a resting state exhibit structure-specific temporal correlations along white matter tracts. In this report we validate our preliminary findings and introduce spatio-temporal functional correlation tensors to characterize the directional preferences of temporal correlations in MRI signals acquired at rest. The results bear a remarkable similarity to data obtained by diffusion tensor imaging but without any diffusion-encoding gradients. Just as in gray matter, temporal correlations in resting state signals may reflect intrinsic synchronizations of neural activity in white matter. Here we demonstrate that functional correlation tensors are able to visualize long range white matter tracts as well as short range sub-cortical fibers imaged at rest, and that evoked functional activities alter these structures and enhance the visualization of relevant neural circuitry. Furthermore, we explore the biophysical mechanisms underlying these phenomena by comparing pulse sequences, which suggest that white matter signal variations are consistent with hemodynamic (BOLD) changes associated with neural activity. These results suggest new ways to evaluate MRI signal changes within white matter.
Magnetic Resonance Imaging 10/2015; DOI:10.1016/j.mri.2015.10.003 · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver glycogen represents an important physiological form of energy storage. It plays a key role in the regulation of blood glucose concentrations and dysregulations in hepatic glycogen metabolism are linked to many diseases including diabetes and insulin resistance. In this work we develop, optimize, and validate a non-invasive protocol to measure glycogen levels in isolated perfused mouse livers using Chemical Exchange Saturation Transfer (CEST) NMR spectroscopy. Model glycogen solutions were used to determine optimal saturation pulse parameters which were then applied to intact perfused mouse livers of varying glycogen content. Glycogen measurements from serially acquired CEST Z-spectra of livers were compared with measurements from interleaved natural abundance 13C NMR spectra. Experimental data revealed that CEST-based glycogen measurements were highly correlated with 13C NMR glycogen spectra. Monte Carlo simulations were then used to investigate the inherent (i.e. signal to noise based) errors in the quantification of glycogen with each technique. This revealed that CEST was intrinsically more precise than 13C NMR, although in practice may be prone to other errors induced by variations in experimental conditions. We also observed that the CEST signal from glycogen in liver was significantly less than that observed from identical amounts in solution. Our results demonstrate that CEST provides an accurate, precise, and readily accessible method to non-invasively measure liver glycogen levels and their changes. Furthermore this technique can be used to map glycogen distributions via conventional proton magnetic resonance imaging - a capability universally available on clinical and pre-clinical MRI scanners vs. 13C detection, which is limited to a small fraction of clinical-scale MRI scanners.
[Show abstract][Hide abstract] ABSTRACT: Recent demonstrations of correlated low-frequency MRI signal variations between subregions of the spinal cord at rest in humans, similar to those found in the brain, suggest that such resting-state functional connectivity constitutes a common feature of the intrinsic organization of the entire central nervous system. We report our detection of functional connectivity within the spinal cords of anesthetized squirrel monkeys at rest and show that the strength of connectivity within these networks is altered by the effects of injuries. By quantifying the low-frequency MRI signal correlations between different horns within spinal cord gray matter, we found distinct functional connectivity relationships between the different sensory and motor horns, a pattern that was similar to activation patterns evoked by nociceptive heat or tactile stimulation of digits. All horns within a single spinal segment were functionally connected, with the strongest connectivity occurring between ipsilateral dorsal and ventral horns. Each horn was strongly connected to the same horn on neighboring segments, but this connectivity reduced drastically along the spinal cord. Unilateral injury to the spinal cord significantly weakened the strength of the intrasegment horn-to-horn connectivity only on the injury side and in slices below the lesion. These findings suggest resting-state functional connectivity may be a useful biomarker of functional integrity in injured and recovering spinal cords.
Proceedings of the National Academy of Sciences 04/2015; 112(19). DOI:10.1073/pnas.1424106112 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To develop and evaluate a new method for detecting calcium deposits using their characteristic magnetic susceptibility effects on magnetic resonance (MR) images at high fields and demonstrate its potential in practice for detecting breast microcalcifications.
Characteristic dipole signatures of calcium deposits were detected in magnetic resonance phase images by computing the cross-correlation between the acquired data and a library of templates containing simulated phase patterns of spherical deposits. The influence of signal-to-noise ratio and various other MR parameters on the results were assessed using simulations and validated experimentally. The method was tested experimentally for detection of calcium fragments within gel phantoms and calcium-like inhomogeneities within chicken tissue at 7 T with optimized MR acquisition parameters. The method was also evaluated for detection of simulated microcalcifications, modeled from biopsy samples of malignant breast cancer, inserted in silico into breast magnetic resonance imaging (MRIs) of healthy subjects at 7 T. For both assessments of calcium fragments in phantoms and biopsy-based simulated microcalcifications in breast MRIs, receiver operator characteristic curve analyses were performed to determine the cross-correlation index cutoff, for achieving optimal sensitivity and specificity, and the area under the curve (AUC), for measuring the method's performance.
The method detected calcium fragments with sizes of 0.14-0.79 mm, 1 mm calcium-like deposits, and simulated microcalcifications with sizes of 0.4-1.0 mm in images with voxel sizes between (0.2 mm)(3) and (0.6 mm)(3). In images acquired at 7 T with voxel sizes of (0.2 mm)(3)-(0.4 mm)(3), calcium fragments (size 0.3-0.4 mm) were detected with a sensitivity, specificity, and AUC of 78%-90%, 51%-68%, and 0.77%-0.88%, respectively. In images acquired with a human 7 T scanner, acquisition times below 12 min, and voxel sizes of (0.4 mm)(3)-(0.6 mm)(3), simulated microcalcifications with sizes of 0.6-1.0 mm were detected with a sensitivity, specificity, and AUC of 75%-87%, 54%-87%, and 0.76%-0.90%, respectively. However, different microcalcification shapes were indistinguishable.
The new method is promising for detecting relatively large microcalcifications (i.e., 0.6-0.9 mm) within the breast at 7 T in reasonable times. Detection of smaller deposits at high field may be possible with higher spatial resolution, but such images require relatively long scan times. Although mammography can detect and distinguish the shape of smaller microcalcifications with superior sensitivity and specificity, this alternative method does not expose tissue to ionizing radiation, is not affected by breast density, and can be combined with other MRI methods (e.g., dynamic contrast-enhanced MRI and diffusion weighted MRI), to potentially improve diagnostic performance.
Medical Physics 03/2015; 42(3):1436. DOI:10.1118/1.4908009 · 2.64 Impact Factor