Biomedical subjects

Brian K Rutt

Publications and source records attributed to Brian K Rutt.

At least 19 recordsLinked to original sources

PubMed2006

Segmentation of thalamic nuclei using a modified k-means clustering algorithm and high-resolution quantitative magnetic resonance imaging at 1.5 T.

Patient outcome in minimally invasive stereotactic neurosurgical procedures depends on the ability to accurately locate the desired functional region within the deep brain while avoiding the surrounding anatomy. Due to the lack of sufficient contrast within this region in pre-operatively acquired MR images, electrophysiological exploration and histological atlases are currently required to define the surgical target within the thalamus in the treatment of many motor-control disorders. In this paper we introduce a method for segmenting the individual thalamic nuclei based on high-resolution quantitative magnetic resonance images, providing improved target visualization. The method was tested using whole-brain T1 and T2 data acquired from four healthy individuals. Accuracy of the segmentation results was assessed by comparing the center-of-mass coordinates of the segmented nuclei, with coordinates obtained from a classic histological atlas registered to these images. Strong agreement was found, with an average Euclidean distance difference of less than 4.5 mm averaged across all nuclei and all individuals. Reproducibility of the method, determined by calculating the percent similarity of segmentation results derived from data acquired from repeated scan sessions, was greater than 85%. These results illustrate the ability to accurately and reliably segment the primary nuclei of the thalamus and suggest that the method may have utility in the study of individual nuclear regions in disease state as well as for planning deep-brain surgical procedures.

Adult↗

PubMed2006

Synthetic T1-weighted brain image generation with incorporated coil intensity correction using DESPOT1.

The increased use of phased-array and surface coils in magnetic resonance imaging, the push toward increased field strength and the need for standardized imaging across multiple sites during clinical trials have resulted in the need for methods that can ensure consistency of intensity both within the image and across multiple subjects/sites. Here, we describe a means of addressing these concerns through an extension of the rapid T(1) mapping technique - driven equilibrium single-pulse observation of T(1). The effectiveness of the proposed approach was evaluated using human brain T(1) maps acquired at 1.5 T with a multichannel phased-array coil. Corrected "synthetic" T(1)-weighted images were reconstructed by substituting the T(1) values back into the governing signal intensity equation while assuming a constant value for the equilibrium magnetization. To demonstrate signal normalization across a longitudinal study, we calculated synthetic T(1)-weighted images from data acquired from the same healthy subject at four different time points. Signal intensity profiles between the acquired and synthetic images were compared to determine the improvements with our proposed approach. Following correction, the images demonstrate obvious qualitative improvement with increased signal uniformity across the image. Near-perfect signal normalization was also observed across the longitudinal study, allowing direct comparison between the images. In addition, we observe an increase in contrast-to-noise ratio (compared with regular T(1)-weighted images) for synthetic images created, assuming uniform proton density throughout the volume. The proposed approach permits rapid correction for signal intensity inhomogeneity without significantly lengthening exam time or reducing image signal-to-noise ratio. This technique also provides a robust method for signal normalization, which is useful in multicenter longitudinal MR studies of disease progression, and allows the user to reconstruct T(1)-weighted images with arbitrary T(1) weighting.

Artifacts↗

PubMed2006

Semi-automated segmentation and quantification of adipose tissue in calf and thigh by MRI: a preliminary study in patients with monogenic metabolic syndrome.

BACKGROUND: With the growing prevalence of obesity and metabolic syndrome, reliable quantitative imaging methods for adipose tissue are required. Monogenic forms of the metabolic syndrome include Dunnigan-variety familial partial lipodystrophy subtypes 2 and 3 (FPLD2 and FPLD3), which are characterized by the loss of subcutaneous fat in the extremities. Through magnetic resonance imaging (MRI) of FPLD patients, we have developed a method of quantifying the core FPLD anthropometric phenotype, namely adipose tissue in the mid-calf and mid-thigh regions. METHODS: Four female subjects, including an FPLD2 subject (LMNA R482Q), an FPLD3 subject (PPARG F388L), and two control subjects were selected for MRI and analysis. MRI scans of subjects were performed on a 1.5T GE MR Medical system, with 17 transaxial slices comprising a 51 mm section obtained in both the mid-calf and mid-thigh regions. Using ImageJ 1.34 n software, analysis of raw MR images involved the creation of a connectedness map of the subcutaneous adipose tissue contours within the lower limb segment from a user-defined seed point. Quantification of the adipose tissue was then obtained after thresholding the connected map and counting the voxels (volumetric pixels) present within the specified region. RESULTS: MR images revealed significant differences in the amounts of subcutaneous adipose tissue in lower limb segments of FPLD3 and FPLD2 subjects: respectively, mid-calf, 15.5% and 0%, and mid-thigh, 25.0% and 13.3%. In comparison, old and young healthy controls had values, respectively, of mid-calf, 32.5% and 26.2%, and mid-thigh, 52.2% and 36.1%. The FPLD2 patient had significantly reduced subcutaneous adipose tissue compared to FPLD3 patient. CONCLUSION: Thus, semi-automated quantification of adipose tissue of the lower extremity can detect differences between individuals of various lipodystrophy genotypes and represents a potentially useful tool for extended quantitative phenotypic analysis of other genetic metabolic disorders.

Journal Article↗

PubMed2006

In vivo magnetic resonance imaging of single cells in mouse brain with optical validation.

In the current work we demonstrate, for the first time, that single cells can be detected in mouse brain in vivo using magnetic resonance imaging (MRI). Cells were labeled with superparamagnetic iron oxide nanoparticles and injected into the circulation of mice. Individual cells trapped within the microcirculation of the brain could be visualized with high-resolution MRI using optimized MR hardware and the fast imaging employing steady state acquisition (FIESTA) pulse sequence on a 1.5 T clinical MRI scanner. Single cells appear as discrete signal voids on MR images. Direct optical validation was provided by coregistering signal voids on MRI with single cells visualized using high-resolution confocal microscopy. This work demonstrates the sensitivity of MRI for detecting single cells in small animals for a wide range of application from stem cell to cancer cell tracking.

Animals↗

PubMed2006

Cellular MRI contrast via coexpression of transferrin receptor and ferritin.

Recently there has been growing interest in the development and use of iron-based contrast agents for cellular imaging with MRI. In this study we investigated coexpression of the transferrin receptor and ferritin genes to induce cellular contrast in a biological system. Expression of transgenic human transferrin receptor and human ferritin H-subunit was induced in a stably transfected mouse neural stem cell line. When grown in iron-rich medium, the transgenic cells accumulated significantly more iron than control cells, with a trend toward an increase in reactive oxygen species, but no detrimental effects on cell viability. This cellular iron significantly increased the transverse relaxivities, R2 and R2*, at 1.5 T and 7 T. By comparing measurements in the same cell samples at 1.5 T and 7 T, we confirmed the expected increase in relaxivity with increasing field strength. Finally, supplemented transgenic cells transplanted into mouse brain demonstrated increased contrast with surrounding neural tissue on T2*-weighted MR brain images compared to controls. These results indicate that dual expression of proteins at different critical points in the iron metabolism pathway may improve cellular contrast without compromising cell viability.

Animals↗

PubMed2006

Resolution and SNR effects on carotid plaque classification.

Multicontrast-weighted MRI, which is increasingly being used in combination with automatic classification algorithms, has the potential to become a powerful tool for assessing plaque composition. The current literature, however, does not address the relationship between imaging conditions and segmentation viability well. In this study 13 carotid endarterectomy samples were imaged with a 156-microm in-plane resolution and high signal-to-noise ratio (SNR) using proton density (PD), T1, T2, and diffusion weightings. The maximum likelihood (ML) algorithm was used to classify plaque components, with sets of three contrast weighting intensities used as features. The resolution and SNR of the images were then degraded. Classification accuracy was found to be independent of in-plane resolution between 156 microm and 1250 microm, but dependent on SNR. Accuracy decreased less than 10% for degradation in SNR down to 25% of original values, and decreased sharply thereafter. The robustness of automatic classifiers makes them applicable to a wide range of imaging conditions, including standard in vivo carotid imaging scenarios.

Algorithms↗

PubMed2006

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.

Animals↗

PubMed2005

Validation of automatically classified magnetic resonance images for carotid plaque compositional analysis.

BACKGROUND AND PURPOSE: MRI may be used for noninvasive assessment of atherosclerotic lesions; however, MRI evaluation of plaque composition requires validation against an accepted reference standard, such as the American Heart Association (AHA) lesion grade, defined by histopathological examination. METHODS: Forty-eight carotid endarterectomy specimen cross-sections had AHA lesion grade determined histopathologically and were concurrently imaged using combinations of 8 MRI contrast weightings in vitro. A maximum likelihood classification algorithm generated MRI "maps" of plaque components, and an AHA lesion grade was assigned correspondingly. Additional analyses compared classification accuracy obtained with a commonly used set of magnetic resonance contrast weightings [proton density (PDw), T1 (T1w), and partial T2 (T2w)] to accuracy obtained with the combination of PDw, T1w, and diffusion-weighted (Dw) contrast. RESULTS: For the 8-contrast combination, the sensitivities for fibrous tissue, necrotic core, calcification, and hemorrhage detection were 83%, 67%, 86%, and 77%, respectively. The corresponding specificities were 81%, 78%, 99%, and 97%. Good agreement (79%) between magnetic resonance and histopathology for AHA classification was achieved. For the PDw, T1w, and Dw combination, the overall classification accuracy was insignificantly different at 78%, whereas the overall classification accuracy using PDw, T1w, and partial T2w contrast weightings was significantly lower at 67%. CONCLUSIONS: This study provides proof-of-principle that the composition of atherosclerotic plaques determined by automated classification of high-resolution ex vivo MRI accurately reflects lesion composition defined by histopathological examination.

Atherosclerosis↗

PubMed2005

Variation in the carotid bifurcation geometry of young versus older adults: implications for geometric risk of atherosclerosis.

BACKGROUND AND PURPOSE: Retrospective analysis of clinical data has demonstrated major variations in carotid bifurcation geometry, in support of the notion that an individual's vascular anatomy or local hemodynamics may influence the development of atherosclerosis. On the other hand, anecdotal evidence suggests that vessel geometry is more homogenous in youth, which would tend to undermine this geometric risk hypothesis. The purpose of our study was to test whether the latter is indeed the case. METHODS: Cross-sectional images of the carotid bifurcations of 25 young adults (24+/-4 years) and a control group of 25 older subjects (63+/-10 years) were acquired via MRI. Robust and objective techniques were developed to automatically characterize the 3D geometry of the bifurcation and the relative dimensions of the internal, external, and common carotid arteries (ICA, ECA, and CCA, respectively). RESULTS: Young vessels exhibited significantly less interindividual variation in the following geometric parameters: bifurcation angle (48.5+/-6.3 degrees versus 63.6+/-15.4 degrees); ICA angle (21.6+/-6.7 degrees versus 29.2+/-11.3 degrees); CCA tortuosity (0.010+/-0.003 versus 0.014+/-0.011); ICA tortuosity (0.025+/-0.013 versus 0.086+/-0.105); ECA/CCA diameter ratio (0.81+/-0.06 versus 0.75+/-0.13), ICA/CCA (0.81+/-0.06 versus 0.77+/-0.12) diameter ratio, and bifurcation area ratio (1.32+/-0.15 versus 1.19+/-0.35). CONCLUSIONS: The finding of more modest interindividual variations in young adults suggests that, if there is a geometric risk for atherosclerosis, its early detection may prove challenging. Taken together with the major interindividual variations seen in older vessels, it suggests a more complex interrelationship between vascular geometry, local hemodynamics, vascular aging, and atherosclerosis, the elucidation of which now calls for prospective studies.

Adult↗

PubMed2005

Visualization of thalamic nuclei on high resolution, multi-averaged T1 and T2 maps acquired at 1.5 T.

The ability to differentiate noninvasively between the primary nuclear divisions of the thalamus has immediate clinical applicability for surgical planning and guidance of functional stereotactic procedures. Comparison of prior qualitative magnetic resonance imaging (MRI) studies carried out at field strengths of 1.5 and 4 Tesla have revealed contrast within the thalamus that varies with field strength, suggesting possible differences in the inherent T1 and T2 relaxation times of the constituent nuclei. We investigate this hypothesis through acquisition of high-resolution, multi-averaged deep-brain T1 and T2 maps of a healthy volunteer. Fourteen nuclei were identified using their center-of-mass coordinates (in Talairach space) and average T1 and T2 values obtained from regions of interest placed within each. Results from this analysis revealed significant differences in T1 and T2 between the nuclei with a T1 range from 700 to 1,400 ms and a T2 range from 89 to 122 ms, allowing visual discrimination between the major nuclei groups. Furthermore, the high-resolution images showed distinct borders of T1 and T2 hypointensity surrounding each nucleus, revealing structure not reported previously. These results confirm our hypothesis and demonstrate the potential high-resolution quantitative imaging for nucleus visualization and surgical planning.

Brain Mapping↗

PubMed2005

Multisite trial of MR flow measurement: phantom and protocol design.

PURPOSE: To describe a portable, easily assembled phantom with well-defined bore geometry together with a series of tests that will form the basis of a standardized quality assurance protocol in a multicenter trial of flow measurement by the MR phase mapping technique. MATERIALS AND METHODS: The phantom consists of silicone polymer layers containing parallel straight and stenosed flow channels in one layer and a U-bend in a second layer, separated by hermetically sealed agarose slabs. The phantom is constructed by casting low melting-point metal in an aluminum mold precisely milled to the desired geometry, and then using the low melting-point metal core as a negative around which the silicone is allowed to set. By melting out the metal, the flow channels are established. The milled aluminum mold is reusable, ensuring faithful reproduction of the flow geometry for all phantoms thus produced. The agarose layers provide additional loading and static background signal for background correction. With the use of the described phantom, one can evaluate flow measurement accuracy and repeatability, as well as the influence of several imaging geometry factors: slice offset, in-plane position, and slice-flow obliquity. RESULTS: The new phantom is compact and portable, and is well suited for reassembly. We were able to demonstrate its facility in a battery of tests of interest in evaluating MR flow measurements. CONCLUSION: The phantom is a robust standardized test object for use in a multicenter trial. Such a trial, to investigate the performance of MR flow measurement using the phantom and the tests we describe, has been initiated.

Blood Flow Velocity↗

PubMed2005

Anthropometric data for magnetic resonance imaging of the carotid bifurcation.

PURPOSE: To provide anthropometric data applicable to the design of protocols for high-resolution magnetic resonance imaging (MRI) of the carotid bifurcation, particularly those aimed at elucidating the role of local factors in carotid atherogenesis. MATERIALS AND METHODS: Axial black-blood MR images of the carotid bifurcation were acquired from 25 young, healthy volunteers and 25 older, asymptomatic patients, from which were measured a variety of quantities related to the orientation and placement of the bifurcation within the neck. RESULTS: Descriptive statistics were obtained for the following quantities: separation of the bifurcation apices within (57.8+/-6.7 mm) and between (4.9+/-4.1 mm) axial slices; orientation of the bifurcation within the axial plane (31.7+/-26.9 degrees ), and of the common carotid artery (CCA) relative to the sagittal (7.5+/-7.1 degrees ) and coronal (7.9+/-7.8 degrees ) planes; depth of the bifurcation from the skin surface (29.5+/-7.2 mm); and neck width (125.9+/-14.4 mm). CONCLUSION: In most cases, both carotid arteries may be captured, without aliasing, within a 12-cm field-of-view axial image; however, the two apices will rarely be captured within the same axial slice. The CCA is significantly oblique to the body axis, but at angles sufficiently acute to permit the use of axial slices. Finally, a significant linear relationship between neck width and carotid depth may be used to inform radio frequency (RF) coil selection prior to scanning a subject, and hence facilitate optimal imaging in light of the wide anatomic variations observed.

Adult↗

PubMed2005

High-resolution T1 and T2 mapping of the brain in a clinically acceptable time with DESPOT1 and DESPOT2.

Variations in the intrinsic T(1) and T(2) relaxation times have been implicated in numerous neurologic conditions. Unfortunately, the low resolution and long imaging time associated with conventional methods have prevented T(1) and T(2) mapping from becoming part of routine clinical evaluation. In this study, the clinical applicability of the DESPOT1 and DESPOT2 imaging methods for high-resolution, whole-brain, T(1) and T(2) mapping was investigated. In vivo, 1-mm(3) isotropic whole-brain T(1) and T(2) maps of six healthy volunteers were acquired at 1.5 T with an imaging time of <17 min each. Isotropic maps (0.34 mm(3)) of one volunteer were also acquired (time <21 min). Average signal-to-noise within the 1-mm(3) T(1) and T(2) maps was approximately 20 and approximately 14, respectively, with average repeatability standard deviations of 46.7 ms and 6.7 ms. These results demonstrate the clinical feasibility of the methods in the study of neurologic disease.

Brain↗

PubMed2005

Detection threshold of single SPIO-labeled cells with FIESTA.

MRI of superparamagnetic iron oxide (SPIO)-labeled cells has become a valuable tool for studying the in vivo trafficking of transplanted cells. Cellular detection with MRI is generally considered to be orders of magnitude less sensitive than other techniques, such as positron emission tomography (PET), single photon emission-computed tomography (SPECT), or optical fluorescence microscopy. However, an analytic description of the detection threshold for single SPIO-labeled cells and the parameters that govern detection has not been adequately provided. In the present work, the detection threshold for single SPIO-labeled cells and the effect of resolution and SNR were studied for a balanced steady-state free precession (SSFP) sequence (3D-FIESTA). Based on the results from both theoretical and experimental analyses, an expression that predicts the minimum detectable mass of SPIO (m(c)) required to detect a single cell against a uniform signal background was derived: m(c) = 5v/(K(fsl) x SNR), where v is the voxel volume, SNR is the image signal-to-noise ratio, and K(fsl) is an empirical constant measured to be 6.2 +/- 0.5 x 10(-5) microl/pgFe. Using this expression, it was shown that the sensitivity of MRI is not very different from that of PET, requiring femtomole quantities of SPIO iron for detection under typical micro-imaging conditions (100 microm isotropic resolution, SNR = 60). The results of this work will aid in the design of cellular imaging experiments by defining the lower limit of SPIO labeling required for single cell detection at any given resolution and SNR.

Cell Count↗

PubMed2004

Determination of optimal angles for variable nutation proton magnetic spin-lattice, T1, and spin-spin, T2, relaxation times measurement.

T1 and T2 can be rapidly determined with a combination of multiangle spoiled gradient recalled echo (SPGR) and steady-state free precession (SSFP) imaging. Previously, we demonstrated a simple method for determining the set of SPGR and SSFP angles that provided greater T1 and T2 precision than a set of uniformly spaced angles. In this article a more rigorous approach for determining angles is described. Weighted least-squares is also introduced for T1 and T2 estimation and a novel weighting function described. This new approach, suited for imaging applications where large T1 and T2 ranges are anticipated, provides high and uniform precision over a wide range of T1 and T2 values.

Algorithms↗

PubMed2004

Quantitative diffusion imaging with steady-state free precession.

The addition of a single, unbalanced diffusion gradient to the steady-state free precession (SSFP) imaging sequence sensitizes the resulting signal to free diffusion. Unfortunately, the confounding influence of both longitudinal (T1) and transverse (T2) relaxation on the diffusion-weighted SSFP (dwSSFP) signal has made it difficult to quantitatively determine the apparent diffusion coefficient (ADC). Here, a multistep method in which the T1, T2, and spin density (Mo) constants are first determined using a rapid mapping technique described previously is presented. Quantitative ADC can then be determined through a novel inversion of the appropriate signal model. The accuracy and precision of our proposed method (which we term DESPOD) was determined by comparing resulting ADC values from phantoms to those calculated from traditional diffusion-weighted echo planar imaging (dwEPI) images. Error within the DESPOD-derived ADC maps was found to be less than 3%, with good precision over a biologically relevant range of ADC values.

Algorithms↗

PubMed2004

Rapid T2 estimation with phase-cycled variable nutation steady-state free precession.

Variable nutation SSFP (DESPOT2) permits rapid, high-resolution determination of the transverse (T2) relaxation constant. A limitation of DESPOT2, however, is the presence of T2 voids due to off-resonance banding artifacts associated with SSFP images. These artifacts typically occur in images acquired with long repetition times (TR) in the presence of B0 inhomogeneities, or near areas of magnetic susceptibility difference, such that the transverse magnetization experiences a net phase shift during the TR interval. This places constraints on the maximum spatial resolution that can be achieved without artifact. Here, a novel implementation of DESPOT2 is presented incorporating RF phase-cycling which acts to shift the spatial location of the bands, allowing reconstruction of a single, reduced artifact-image. The method is demonstrated in vivo with the acquisition of a 0.34 mm3 isotropic resolution T2 map of the brain with high precision and accuracy and significantly reduced artifact.

Brain↗

PubMed2004

Atherosclerotic plaque characterization by MR imaging.

The MR imaging of carotid artery and aortic plaque has undergone significant improvement in the last decade. Early studies utilizing ex vivo specimens and spin echo or fast spin echo imaging, led to the conclusion that T2-weighting was the best single contrast to characterize carotid plaque morphology. On these images, the fibrous plaque appears bright and the lipid core is dark; thrombus can have variable intensity. There can be an overlap in T2w signal intensities among the various plaque components, which can be partially offset by the use of qualitative or multi-spectral analysis of multiple contrast images. With improvements in coil design, sequence design, main field and gradient capabilities, accurate in vivo differentiation and measurement of these various plaque components should be possible in a few years. Carotid and aortic plaque burden can be accurately measured in vivo today; ongoing longitudinal studies should lead to a better understanding of the relationship between plaque burden and the risk of thromboembolic complications, as well as the effect of diet and drug therapy in hyperlipidemic patients. With these developments in place or soon to be available, MR imaging of the diseased carotid artery and aortic wall may prove to be even more important than MR angiography or other current clinical tests.

Animals↗