Cortical bone water concentration: dependence of MR imaging measures on age and pore volume fraction.

PURPOSE: To quantify bulk bone water to test the hypothesis that bone water concentration (BWC) is negatively correlated with bone mineral density (BMD) and is positively correlated with age, and to propose the suppression ratio (SR) (the ratio of signal amplitude without to that with long-T2 suppression) as a potentially stronger surrogate measure of porosity, which is evaluated ex vivo and in vivo. MATERIALS AND METHODS: Human subject studies were conducted in compliance with institutional review board and HIPAA regulations. Healthy men and women (n = 72; age range, 20-80 years) were examined with a hybrid radial ultrashort echo time magnetic resonance (MR) imaging sequence at 3.0 T, and BWC was determined in the tibial midshaft. In a subset of 40 female subjects, the SR was measured with a similar sequence. Cortical volumetric BMD (vBMD) was measured by means of peripheral quantitative computed tomography (CT). The method was validated against micro-CT-derived porosity in 13 donor human cortical bone specimens. Associations among parameters were evaluated by using standard statistical tools. RESULTS: BWC was positively correlated with age (r = 0.52; 95% confidence interval [CI]: 0.22, 0.73; P = .002) and negatively correlated with vBMD at the same location (r = -0.57; 95% CI: -0.76, -0.29; P < .001). Data were suggestive of stronger associations with SR (r = 0.64, 95% CI: 0.39, 0.81, P < .001 for age; r = -0.67, 95% CI: -0.82, -0.43, P < .001 for vBMD; P < .001 for both), indicating that SR may be a more direct measure of porosity. This interpretation was supported by ex vivo measurements showing SR to be strongly positively correlated with micro-CT porosity (r = 0.88; 95% CI: 0.64, 0.96; P < .001) and with age (r = 0.87; 95% CI: 0.62, 0.96; P < .001). CONCLUSION: The MR imaging-derived SR may serve as a biomarker for cortical bone porosity that is potentially superior to BWC, but corroboration in larger cohorts is indicated.

Wavelet-transformed temporal cerebral blood flow signals during attempted inhibition of cue-induced cocaine craving distinguish prognostic phenotypes.

BACKGROUND: Cocaine addicted patients with positive cocaine urine status at treatment entry are far less likely to have a successful treatment outcome. This work aims to identify brain substrates that can distinguish this group of patients from their cocaine-negative counterparts in order to better understand this clinical phenotype. Going a step beyond conventional functional connectivity, we used wavelet transform coherence (WTC) to determine in which ways the temporal pattern of fMRI cerebral blood flow (CBF) signals during attempted inhibition of cue-induced cocaine craving may differ between these two groups. METHODS: Using a critical node in motivational circuitry, amygdala, as a seed, whole brain correlations for the entire sample revealed a functional connection with the dorsal cingulate. Next, WTC maps of CBF were constructed for each individual, characterizing the temporal patterns between these two regions during craving inhibition. RESULTS: As revealed by WTC, during attempted craving inhibition, the cocaine-negative subjects had significantly stronger and longer negative coherence between the amygdala and the dorsal cingulate, as compared to the cocaine-positive subjects. This relationship was neither evident in the resting state nor between two regions unrelated to inhibition processes. CONCLUSIONS: The duration and strength of negative coherence calculated from wavelet-transformed CBF provide an objective and well-defined way to characterize brain responses during attempted inhibition of cue-induced craving, at the level of the individual. The stronger and sustained negative coherence in CBF between motivational (amygdala) and modulatory (dorsal cingulate) regions in cocaine-negative subjects may be a critical brain strength that fosters improved craving inhibition and thus, better clinical outcome.

A GAL4-driver line resource for Drosophila neurobiology.

We established a collection of 7,000 transgenic lines of Drosophila melanogaster. Expression of GAL4 in each line is controlled by a different, defined fragment of genomic DNA that serves as a transcriptional enhancer. We used confocal microscopy of dissected nervous systems to determine the expression patterns driven by each fragment in the adult brain and ventral nerve cord. We present image data on 6,650 lines. Using both manual and machine-assisted annotation, we describe the expression patterns in the most useful lines. We illustrate the utility of these data for identifying novel neuronal cell types, revealing brain asymmetry, and describing the nature and extent of neuronal shape stereotypy. The GAL4 lines allow expression of exogenous genes in distinct, small subsets of the adult nervous system. The set of DNA fragments, each driving a documented expression pattern, will facilitate the generation of additional constructs for manipulating neuronal function.

Performance of the MRI-based virtual bone biopsy in the distal radius: serial reproducibility and reliability of structural and mechanical parameters in women representative of osteoporosis study populations.

Serial reproducibility and reliability critically determine sensitivity to detect changes in response to intervention and provide a basis for sample size estimates. Here, we evaluated the performance of the MRI-based virtual bone biopsy in terms of 26 structural and mechanical parameters in the distal radius of 20 women in the age range of 50 to 75 years (mean=62.0 years, S.D.=8.1 years), representative of typical study populations in drug intervention trials and fracture studies. Subjects were examined three times at average intervals of 20.2 days (S.D.=14.5 days) by MRI at 1.5 T field strength at a voxel size of 137×137×410 µm(3). Methods involved prospective and retrospective 3D image registration and auto-focus motion correction. Analyses were performed from a central 5×5×5 mm(3) cuboid subvolume and trabecular volume consisting of a 13 mm axial slab encompassing the entire medullary cavity. Whole-volume axial stiffness and sub-regional Young's and shear moduli were computed by finite-element analysis. Whole-volume-derived aggregate mean coefficient of variation of all structural parameters was 4.4% (range 1.8% to 7.7%) and 4.0% for axial stiffness; corresponding data in the subvolume were 6.5% (range 1.6% to 13.0%) for structural, and 5.5% (range 4.6% to 6.5%) for mechanical parameters. Aggregate ICC was 0.976 (range 0.947 to 0.986) and 0.992 for whole-volume-derived structural parameters and axial stiffness, and 0.946 (range 0.752 to 0.991) and 0.974 (range 0.965 to 0.978) for subvolume-derived structural and mechanical parameters, respectively. The strongest predictors of whole-volume axial stiffness were BV/TV, junction density, skeleton density and Tb.N (R(2) 0.79-0.87). The same parameters were also highly predictive of sub-regional axial modulus (R(2) 0.88-0.91). The data suggest that the method is suited for longitudinal assessment of the response to therapy. The underlying technology is portable and should be compatible with all general-purpose MRI scanners, which is appealing considering the very large installed base of this modality.

Auto-tracking system for human lumbar motion analysis.

Previous lumbar motion analyses suggest the usefulness of quantitatively characterizing spine motion. However, the application of such measurements is still limited by the lack of user-friendly automatic spine motion analysis systems. This paper describes an automatic analysis system to measure lumbar spine disorders that consists of a spine motion guidance device, an X-ray imaging modality to acquire digitized video fluoroscopy (DVF) sequences and an automated tracking module with a graphical user interface (GUI). DVF sequences of the lumbar spine are recorded during flexion-extension under a guidance device. The automatic tracking software utilizing a particle filter locates the vertebra-of-interest in every frame of the sequence, and the tracking result is displayed on the GUI. Kinematic parameters are also extracted from the tracking results for motion analysis. We observed that, in a bone model test, the maximum fiducial error was 3.7%, and the maximum repeatability error in translation and rotation was 1.2% and 2.6%, respectively. In our simulated DVF sequence study, the automatic tracking was not successful when the noise intensity was greater than 0.50. In a noisy situation, the maximal difference was 1.3 mm in translation and 1° in the rotation angle. The errors were calculated in translation (fiducial error: 2.4%, repeatability error: 0.5%) and in the rotation angle (fiducial error: 1.0%, repeatability error: 0.7%). However, the automatic tracking software could successfully track simulated sequences contaminated by noise at a density ≤ 0.5 with very high accuracy, providing good reliability and robustness. A clinical trial with 10 healthy subjects and 2 lumbar spondylolisthesis patients were enrolled in this study. The measurement with auto-tacking of DVF provided some information not seen in the conventional X-ray. The results proposed the potential use of the proposed system for clinical applications.

Quantifying cortical bone water in vivo by three-dimensional ultra-short echo-time MRI.

Bone contains a significant fraction of water that is not detectable with ordinary Cartesian imaging sequences. The advent of ultra-short echo-time (UTE) methods has allowed the recovery of this submillisecond T(2)* water. In this work, we have developed a new three-dimensional hybrid-radial ultra-short echo-time (3D HRUTE) imaging technique based on slab selection by means of half-sinc pulses, variable-TE slice encoding and algorithms for quantification. The protocol consists of collecting two datasets differing in TR, from which T(1) is extracted, which is needed for quantification. Unlike T(2)*, which has been found to vary within a narrow range and does not require individual correction, T(1) is critically subject dependent (range, 100-350 ms). No soft-tissue suppression was used to preserve the signal-to-noise ratio of the short-T(2) bone water protons or to minimize the loss of relatively mobile water in large pores. Critical for quantification is correction for spatial variations in reception field and selection of the endosteal boundary for inclusion of pixels in the bone water calculation, because of the ruffled boundary stemming from trabecularization of the endosteal surface. The reproducibility, evaluated in 10 subjects covering the age range 30-80 years, yielded an average coefficient of variation of 4.2% and an intraclass correlation coefficient of 0.95, suggesting that a treatment effect on the order of 5% could be detected in as few as 10 subjects. Lastly, experiments in specimens by means of graded deuterium exchange showed that approximately 90% of the detected signal arises from water protons, whose relaxation rates (1/T(1) and 1/T(2)*) scale linearly with the isotopic volume fraction of light water after stepwise exchange with heavy water. The data thus show conclusively that the method quantifies water even though, in vivo, no distinction can be made between various fractions, such as collagen-bound vs pore-resident water.

Segmentation of center brains and optic lobes in 3D confocal images of adult fruit fly brains.

Automatic alignment (registration) of 3D images of adult fruit fly brains is often influenced by the significant displacement of the relative locations of the two optic lobes (OLs) and the center brain (CB). In one of our ongoing efforts to produce a better image alignment pipeline of adult fruit fly brains, we consider separating CB and OLs and align them independently. This paper reports our automatic method to segregate CB and OLs, in particular under conditions where the signal to noise ratio (SNR) is low, the variation of the image intensity is big, and the relative displacement of OLs and CB is substantial. We design an algorithm to find a minimum-cost 3D surface in a 3D image stack to best separate an OL (of one side, either left or right) from CB. This surface is defined as an aggregation of the respective minimum-cost curves detected in each individual 2D image slice. Each curve is defined by a list of control points that best segregate OL and CB. To obtain the locations of these control points, we derive an energy function that includes an image energy term defined by local pixel intensities and two internal energy terms that constrain the curve's smoothness and length. Gradient descent method is used to optimize this energy function. To improve both the speed and robustness of the method, for each stack, the locations of optimized control points in a slice are taken as the initialization prior for the next slice. We have tested this approach on simulated and real 3D fly brain image stacks and demonstrated that this method can reasonably segregate OLs from CBs despite the aforementioned difficulties.

Parametric characterization of spinal motions in osteoporotic vertebral fracture at level T12 with fluoroscopy.

Vertebral fractures due to osteoporosis are a common skeletal disorder affecting the mobility of the patients, although little is known about the relationship between spinal kinematics and osteoporotic fracture. The purpose of this study was to characterize the motions of the thoracolumbar spine affected by osteoporotic vertebral fracture at level T12 and compare the results with those of non-fracture osteoporosis subjects. We examined the continuous segmental kinematics of the vertebrae, and describe the segmental motion of the spine when a fracture at T12 is present. Fluoroscopy sequences of the thoracolumbar spines during sagittal and lateral flexion were collected from 16 subjects with osteoporosis of their spine (6 with vertebral fractures at T12, 10 without a fracture). Vertebrae T10-L2 in each frame of the sequences were landmarked. Kinematic parameters were calculated based on the landmarks and motion graphs were constructed. Compared to the control subjects who did not have a fracture, fracture subjects had a more asymmetric lateral range of motion (RoM) and required a longer time to complete certain phases of the motion cycle which are parameterized as lateral flexion ratio and percentage of motion cycle, respectively. Prolonged deflection was more frequently found from the fracture group. Characterizing the motions of the fractured vertebra together with its neighboring vertebrae with these kinematic parameters is useful in quantifying the dysfunction and may be a valuable aid to tracking progress of treatment.