Browsing by Subject "Magnetic Resonance Imaging"
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Item 3 Tesla Magnetic Resonance Imaging of Hippocampal Asymmetry: Results from the Dallas Heart Study(2013-08-01) Lucarelli, Richard T.; Peschock, Ronald M.Keywords: hippocampal asymmetry, hippocampus freesurfer fsl, mesial temporal sclerosis, temporal lobe ipilepsy Background Asymmetry of the hippocampus is regarded as an important clinical finding but limited data on hippocampal asymmetry is available for the general population. Here we present hippocampal asymmetry data from the Dallas Heart Study determined by automated methods and its relationship to age, sex, and ethnicity. Methods 3D-MPRAGE MRI were obtained in 2082 DHS-2 participants. The MR images were analyzed using two standard automated brain segmentation programs, FSL-FIRST and Freesurfer. Individuals with imaging error, self-reported stroke, or major structural abnormalities were excluded. Statistical analyses were performed to determine significance of the findings across age, sex, and ethnicity. Results At the 90th percentile FSL-FIRST demonstrated hippocampal asymmetry of 9.8% (95% CI 9.3 to 10.5%). The 90th percentile of hippocampal asymmetry measured by the difference between hippocampii over the larger hippocampus was 17.9% (95% CI 17.0 to 19.1%). Hippocampal asymmetry increases with age (P=0.0216) and men have greater asymmetry than women as shown by FSL-FIRST (P=0.0036), but ethnicity is not significantly correlated with asymmetry. To confirm these findings Freesurfer was used. Freesurfer showed asymmetry of 4.4% (95% CI 4.3 to 4.7%) normalized to total volume, and 8.5% (95% CI 8.3 to 9.0%) when normalized by difference/larger hippocampus. Freesurfer also showed that hippocampal asymmetry increases with age (P=0.0024), and that men had greater asymmetry than women (P=0.03). Conclusion There is a significant degree of hippocampal asymmetry in the population. The data provided will aid in the research, diagnosis, and treatment of temporal lobe epilepsy and other neurological diseaseItem Alpha(V)Beta(3)-Targeted Nanoprobes for In Vivo Imaging of Tumor Angiogenesis(2010-11-02T18:20:26Z) Kessinger, Chase William; Gao, JinmingLung cancer is the leading cause of cancer-related deaths in the US and abroad (WHO, 2010). Early detection of the disease has increased patients’ five-year survival rates from 4% to over 50% (NCI SEER, 2010). Angiogenesis plays a critical role in the carcinogenesis and cancer metastasis of solid tumors. Integrin αvβ3 is a well-established overexpressed biomarker of angiogenesis and has recently been exploited in the clinical stratification of different types of cancer. Although magnetic resonance imaging (MRI) is not a first-line clinical imaging modality for the detection and diagnosis of lung cancer, recent advances in theranostic polymeric nanoplatforms and the development of ultrasensitive contrast agents, such as superparamagnetic iron oxide (SPIO) nanoparticles, has greatly broadened the application of MRI in cancer detection and molecular imaging. The objective of this work is to develop superparamagnetic polymeric micelle (SPPM) nanoprobes that can noninvasively image tumor angiogenesis in vivo using conventional T2/T2*-weighted and off-resonance saturation (ORS) MRI methods. Therefore, we hypothesized that the inclusion of an αvβ3-specific ligand, cRGD (cyclic Arg-Gly-Asp) peptide and encapsulation of a cluster of SPIO in the SPPM nanoprobe formulation would allow the specific imaging of tumor angiogenesis. SPPM nanoprobes are small (50-70 nm), and contain a cluster of SPIO in the core while maintaining the micelle core-shell architecture. In vitro examination of αvβ3-targeted cRGD-SPPM demonstrate an increase cellular uptake in αvβ3 overexpressing cells over control SPPM formulations. Upon translation to in vivo subcutaneous lung tumor models in mice, cRGD-SPPM is able to noninvasively image and quantitate tumor angiogenesis and demonstrate in vivo colocalization with αvβ3 integrin. In parallel with SPPM characterization, the ORS imaging method was validated in vitro and was successfully applied in vivo for imaging tumor angiogenesis and demonstrated an increased sensitivity and specificity for SPPM over conventional T2*-weighted MR imaging. Application of high temporal resolution (HTR) - MRI, combined with the ultrasensitivity of the SPPM nanoprobe, allows for the kinetic analysis of cRGD-SPPM targeting to angiogenic regions in vivo. Finally, SPPM shows the ability to detect small lung cancer nodules (<700 μm - 3 mm) in tail-vein induced orthotopic lung cancer models using convention T2-weighted and ORS MRI. The results presented herein, provide the characterization and proof-of-principle experiments that point towards the diagnostic potential of SPPM nanoprobes for the early detection of lung cancer.Item Connectivity within the Default Mode Network after Traumatic Axonal Injury(2011-12-12) Arenivas, Ana; Marquez de la Plata, CarlosTraumatic axonal injury (TAI) is a common consequence of TBI in which the brain’s white matter is mechanically torn by deceleration and rotational forces. Injury to axons after this type of injury causes significant impairments in cognitive functioning, but the association between disruption of structural connections (i.e., axons) and the brain’s functional connectedness is not well understood. Studies examining integrity of white matter after TAI have found significant compromise to structures likely involved in the connectivity of the default mode network (DMN), a reliably elicited functional neural network with clinical implications. The discriminant and prognostic utilities of the DMN following traumatic axonal injury (TAI) have not been previously investigated. This broad investigation was comprised of two related studies examining the utility of neuroimaging modalities as biomarkers of TAI. Resting-state magnetic resonance imaging (RS-MRI) and diffusion tensor imaging (DTI) sequences were acquired 6-11 months post-injury using a 3T scanner from 25 patients with TAI and 17 controls. Functional and neurocognitive outcomes were assessed the same day. The first study examined the utility of three approaches analyzing DMN integrity using RS-fMRI. The purpose was to identify the utility of each approach to distinguish between healthy and brain-injured individuals, and determine whether observed differences have clinical significance. The second study integrated functional and structural connectivity measures of the DMN to determine whether compromise to functional connectivity within this network can be explained by the degree of white matter compromise commonly observed after TAI. The first study concluded that connectivity within the DMN is compromised after TAI, as all three methods demonstrated good ability to discriminate between healthy and injured brains. The second study suggests the functional disconnectedness within the DMN is in part due to compromise in structural connections observed after TAI. Neither the degree of functional or structural compromise to the DMN has clinical implications in TAI. In general, the two investigations suggest the DMN undergoes compromise after TAI, and connectivity between nodes of the network are valid markers of axonal injury.Item Cross-Sectional Differences in Brain Activity Supporting Working Memory(2011-12-12) Dewey, Laura Marie; Motes, Michael A.Cross-sectional developmental studies have shown working memory (WM) to follow monotonic developmental trajectories through childhood into adolescence. In contrast, structural neuroimaging studies have shown that several brain regions, such as the prefrontal cortex (PFC), follow nonlinear developmental trajectories from birth through late adulthood. The present study sought to explore the relationship between functional activation in brain regions supporting WM and age throughout adolescence. Forty-two healthy adolescents (aged 11 to 18) completed a delayed-response WM task while functional magnetic resonance imaging (fMRI) data were collected. Participants studied either one or six letters (3.5 seconds), remembered the items over a delay (5 seconds), and then judged whether a single probe letter was in the studied set (within 2.5 seconds). An fMRI blocked design was used: four blocks per set-size and three trials per block. Additionally, the participants completed the Digit Span subtest from the Wechsler intelligence tests in order to obtain behavioral measures of WM. Hierarchical regression analyses were used to evaluate linear and quadratic relationships between WM task-related signal-change per voxel and age while evaluating the potential mediating effects of WM indices (response time [RT], digit span forward, digit span backward). Linear relationships were found in right medial Brodmann’s Area (BA) 6, right cerebellum, and left BA34 when the linear effects of gender, handedness, response time, digit span forward, and digit span backward were controlled for statistically. Thus, activation increased with age within these regions, but the linear trends were being suppressed by the covariates. Activation on the WM task increased with age in right medial BA6 when the effects of WM indices, as measured in the present study, were removed. The separate relationship between WM capacity and right medial BA6 activation suppressed the detection of the relationship between right medial BA6 activation and age. The data support developmental, possibly maturational, changes in the role of medial PFC in WM that are independent of WM ability measures used in the present study. This finding has implications for broad theories about the development of WM and other cognitive abilities that allow for the identification of both normal and deviant developmental trajectories.Item Dual Process Models of Decision Making: An Fmri Investigation of Framing Effects and Individual Differences(2010-11-02T18:17:38Z) Murch, Kevin Bertrand; Krawczyk, DanielWhile the manifestation of decisions can be explained in several ways, dual-process models provide a unique purview into the relationship between automatic and controlled components of the decision making process. Although dichotomies in processing can be observed utilizing different experimental paradigms, framing effects provide a unique reflection of these dichotomies. Framing effects have been studied behaviorally for quite some time; however, only recently have investigators begun to examine the neurobiological basis for these effects. Additionally, as these effects mirror dual-process accounts of decision making, the examination of concurrent task demands and individual differences in the manifestation of framing effects could serve to inform dual-process models. The current studies examined two different framing paradigms in the context of experimental manipulations, perspective taking and emotional priming, which were intended to facilitate processing within the subsystems of a dual-process account of social cognition. Framing manipulations included both a previously established risky-choice framing paradigm and a novel, socially relevant attribute framing paradigm. In addition to behavioral studies, an fMRI investigation of the attribute framing paradigm was conducted to examine the neural correlates associated with the observed framing effect within the neurobiological framework of the X- and C-System model of social cognition. Finally, the current studies sought to examine the role that individual differences (e.g., personality, intelligence, need for cognition, cognitive reflection, impulsivity, and attachment style) play in susceptibility to framing phenomena. Results indicated the framing manipulations utilized in these studies were successful in eliciting a bias in decision making behavior. The effects of additional experimental manipulations were mixed, with some evidence for influences on the manifestation of the framing effects. fMRI data generally showed changes in brain activity in a manner consistent with the neurobiological divisions included within the X-and C-System model and provided preliminary evidence suggesting differences in the way frames and counterframes are processed. Individual differences, both in terms of psychological constructs and brain activity, appeared to be associated with susceptibility to framing phenomena. In total, the current series of studies provide several novel contributions to the existing literature on framing effects, and by extension, dual-process accounts of decision making.Item fMRI Investigation of an Experimental Executive Function Measure: Comparison of the Texas Card Sorting Test to the Wisconsin Card Sorting Test in Healthy Adults(2006-12-20) Woolston, Dixie J.; Allen, GregAlthough executive functioning is one of the most studied constructs in neuropsychology, it remains one of the most elusive and enigmatic skill sets to measure and understand. The Wisconsin Card Sorting Test (WCST) is commonly used to assess executive functioning, though it has been criticized for its lengthy administration time and negative feedback component. The Texas Card Sorting Test (TCST) was developed as a problem-solving measure to be applied in linguistically diverse samples, and does not have the limitations of the WCST. The overall purpose of the present study was to validate the TCST as a measure of frontal and subcortical function, and to compare the TCST to the WCST. Twenty-five healthy volunteers underwent functional magnetic resonance imaging (fMRI) while performing computerized versions of the WCST and TCST. Significant activations during the TCST were observed in the prefrontal cortex (BA 6, 9, 44-47), the basal ganglia, bilateral parietal areas (BA 7&39), left cingulate gyrus (BA 24, 31,&32), right superior temporal areas (BA 41&22), left parahippocampal and middle temporal gyri, and right occipital lobe (BA 18&19). Compared to the WCST, the TCST showed increased activity bilaterally in the frontal lobe (BA 6&47), right frontal areas (BA 10&11), the caudate, right superior temporal lobe (BA 38, 41, 42), right temporal lobe (BA 22&34), and left occipital lobe (BA 19&31). Behaviorally, no significant correlations were seen between the WCST and TCST performance variables. This research supports the TCST as a measure of frontal-subcortical function. The TCST appears to be particularly sensitive to orbitofrontal/caudate circuitry as well as superior temporal areas, with greater activation overall observed in right cerebral areas. Given the lack of correlation on behavioral performance variables and the distinct differences in neural correlates, the TCST may assess cognitive processes that are different from the WCST. The TCST has promising potential as a clinical neuropsychological instrument.Item Highly Parallel Magnetic Resonance Imaging with a Fourth Gradient Channel for Compensation of RF Phase Patterns(2012-08-20) Bosshard, John 1983-A fourth gradient channel was implemented to provide slice dependent RF coil phase compensation for arrays in dual-sided or "sandwich" configurations. The use of highly parallel arrays for single echo acquisition magnetic resonance imaging allows both highly accelerated imaging and capture of dynamic and single shot events otherwise inaccessible to MRI. When using RF coils with dimensions on the order of the voxel size, the array coil element phase patterns adversely affect image acquisition, requiring correction. This has previously been accomplished using a pulse of the gradient coil, imparting a linear phase gradient across the sample opposite of that due to the RF coil elements. However, the phase gradient due to the coil elements reverses on opposite sides of the coils, preventing gradient-based phase compensation with sandwich arrays. To utilize such arrays, which extend the imaging field of view of this technique, a fourth gradient channel and coil were implemented to simultaneously provide phase compensation of opposite magnitude to the lower and upper regions of a sample, imparting opposite phase gradients to compensate for the opposite RF coil phase patterns of the arrays. The fourth gradient coil was designed using a target field approach and constructed using printed circuit boards. This coil was integrated with an RF excitation coil, dual-sided receive array, and sample loading platform to form a single imaging probe capable of both ultra-fast and high resolution magnetic resonance imaging. By employing the gradient coil, this probe was shown to simultaneously provide improved phase compensation throughout a sample, enabling simultaneous SEA imaging using arrays placed below and above a sample. The fourth gradient coil also improves the acquisition efficiency of highly accelerated imaging using both arrays for receive. The same imaging probe was shown to facilitate accelerated MR microscopy over the field of view of the entire array with no changes to the hardware configuration. The spatio-temporal imaging capabilities of this system were explored with magnetic resonance elastography.Item Magnetic Resonance Imaging of the Heart and Vasculature at 3 Tesla: Novel Strategies for the Diagnosis and Risk Stratification of Cardiovascular Disease(2011-10-03T14:15:07Z) Maroules, Christopher D.; Peshock, Ronald M.Purpose: (1) To study the effects of field strength and parallel imaging on image contrast and the interstudy reproducibility of right and left ventricular (RV and LV) measurements using steady-state free precession (SSFP) cardiac magnetic resonance; (2) to explore the impact of 3T parallel imaging techniques on the assessment and reproducibility of black-blood aortic atherosclerosis imaging; and (3) to evaluate the feasibility of coronary sinus flow imaging by 3T spiral velocity-encoded cine (VEC) MR imaging in overweight women with risk factors for cardiovascular disease Materials and Methods: To evaluate cardiac measurements and aortic atherosclerosis by cardiac magnetic resonance, thirty-two subjects (20 normal, 12 cardiac patients) underwent SSFP cine short-axis imaging and black-blood abdominal aortic imaging: two studies at 1.5T, one study at 3T, and another study at 3T with parallel imaging (SENSE). Contrast-to-noise ratios (CNR) were compared between techniques. To evaluate the feasibility of coronary sinus flow MR imaging, ten women (age 38 years ± 10) with a mean BMI of 33 kg/m2 ± 8 were studied. Coronary sinus flow was measured at baseline and in response to cold pressor stress. Changes in right coronary artery flow were also measured before and after stress using VEC MRI. Results: Cardiac MRI: 3T SENSE imaging reduced cardiac imaging time from 8 ± 2 min to 3 ± 1 min (P<0.001). A significant gain in LV CNR was detected between 1.5T and 3T with SENSE (43.8 ± 6.5 vs 48.4 ± 7.4, P=0.01), but no significant gain was detected in RV CNR. The reproducibility of LV and RV measurements between two 1.5T studies was not significantly different from the reproducibility between a 1.5T study and a 3T study with SENSE. Aortic MRI: Image quality scores were comparable between 1.5-T and 3-T with SENSE (4.0 ± 0.6 vs 4.2 ± 0.6, P = 0.21). Bland-Altman reproducibility for MWT was -0.03 mm ± 0.15 (1.5-T vs 1.5-T) and -0.01 mm ± 0.18 (1.5-T vs 3-T with SENSE), P = 0.83. Detection of the presence of absence of plaque was comparable. Coronary Sinus Flow Imaging: A significant 24% increase in coronary sinus volume flow was observed from baseline to peak cold pressor stress (141 ± 34 ml/min vs. 184 ± 42 ml/min, p = 0.02). Similar increases in RCA flow velocity were observed (15.3 ± 5 cm/sec vs. 23.2 ± 7 cm/sec, P < 0.01). Conclusions: (1) SSFP cardiac MR imaging and black-blood aortic MR imaging are reproducible techniques. (2) Parallel imaging at 3T permits shorter scan time compared to conventional 1.5-T imaging with comparable measurements of cardiac structure and function, as well as aortic atherosclerosis. (3) Coronary sinus spiral velocity-encoded MRI at 3T is a feasible technique for measuring changes in coronary flow in asymptomatic overweight and obese women with risk factors for cardiovascular disease. [Keywords: MRI; 3 Tesla; cardiovascular; imaging; basic stratification]Item Measurement of Cerebral Metabolism and Vascular Function with Magnetic Resonance Imaging(2012-08-13) Xu, Feng; Lu, HanzhangThe brain relies on oxidative metabolism to function properly. Cerebral metabolic rate of oxygen (CMRO2) is thus an important marker for brain health. Existing techniques for quantification of CMRO2 with positron emission tomography (PET) or magnetic resonance imaging (MRI) involve special equipment and/or exogenous agents, and may not be suitable for routine clinical studies. To fill this gap, I developed a noninvasive method for quantifying whole brain CMRO2. This method uses the Fick principle of arterio-venous difference for the calculation of CMRO2.and employs phase-contrast MRI for quantitative blood flow measurement and T2-relaxation-under-spin-tagging (TRUST) MRI for venous oxygenation estimation. During this thesis, I conducted several technical development studies. I first optimized TRUST and phase-contrast MR imaging parameters and demonstrated the ability to measure CMRO2 using completely non-invasive procedures. I further performed calibration and validations studies to show that blood oxygenation measured with TRUST reveals an excellent agreement with the gold standard Pulse Oximetry method. A final technical study was to improve the speed and reliability of TRUST MRI by shortening the scan duration by 60% while reducing the measuring error by half. I have also applied this novel CMRO2 method in better understanding brain physiology in younger and older adults. I studied the effect of CO2 inhalation (also known as hypercapnia) on brain metabolism. A reduced CMRO2 was observed and this effect was further supported by findings using functional connectivity MRI and electroencephalography techniques. I also investigated the effect of O2 modulation (hypoxia and hyperoxia) on brain metabolism and showed a dose dependent effect of O2 concentration on brain activity. Finally, I used this method to assess aged-related differences in brain metabolism and blood supply, and demonstrated a paradoxically higher metabolic rate in older adults, which may be associated with lower neural efficiency in elderly individuals.Item Neural Dysfunction during Decision-Making as a Predictor of Cocaine Relapse(2013-01-17) Braud, Jacquelyn Ashley; Adinoff, Bryon, M.D.Cocaine dependence is a costly disorder characterized by recurrent relapse events. The current investigation used functional magnetic resonance imaging (fMRI) during a decision-making task to predict relapse to drug use in a cocaine-dependent sample. Forty-five treatment-seeking cocaine-dependent subjects, two to four weeks abstinent, and 23 healthy control subjects underwent 3T fMRI. The Response Reversal Task was administered in the scanner to elicit decision-making processes. Individuals were followed for up to six months post-discharge from inpatient substance use treatment to determine time-to-relapse. Seventy-eight percent of the patient sample relapsed an average of 35 days after treatment; ten individuals did not relapse during the follow-up period. No group differences were found between healthy control and cocaine-addicted groups in activation patterns or behavioral measures of decision-making performance. Mean percent BOLD signal change in the patient group was used to identify regions of interest (ROIs) for discriminant analyses to classify patients by short- and long-term relapse. The fMRI activation patterns in the precuneus, bilateral orbitofrontal cortex, left insula, right dorsolateral prefrontal cortex, paracingulate, left hippocampus, and bilateral amygdala correctly classified 71% of patients by short-term and long-term relapse. This investigation suggests that neuroimaging may be a valid predictor of cocaine relapse, which could allow for better individual tailoring of treatment options for improving long-term abstinence.Item Noninvasive Assessment of Tumor Hypoxia Using MRI in Clinical and Preclinical Tumor Models(2013-01-16) Hallac, Rami R.; Mason, Ralph P., Ph.D.Tumor oxygenation influences response to radiation and plays important roles in malignant progression, angiogenesis and metastasis. While methods are available to quantitatively map pO2 dynamics in preclinical studies, new techniques are needed to noninvasively characterize tumor hypoxia and response to interventions in patients. Blood Oxygen Level Dependent (BOLD) MRI based on T2* contrast induced by deoxyhemoglobin concentration [dHb] is sensitive to tumor vascular oxygenation and blood flow. Meanwhile TOLD (Tissue Oxygen Level Dependent) MRI is sensitive to tissue oxygenation based on the shortening of the tissue water T1 due to molecular oxygen [O2]. In this study, I investigate the utility of BOLD and TOLD to evaluate tumor hypoxia in response to breathing hyperoxic gas in rats and test the feasibility of such measurements in patients. All MRI experiments were performed on either a 4.7T small animal Varian or a 3T clinical Philips scanner. Variation in BOLD and TOLD signal response observed in two syngeneic prostate tumor models: Dunning R3327-AT1 and -HI, with respect to oxygen and carbogen breathing were compared with quantitative change in pO2 measured using Fluorocarbon Relaxometry using Echo Planar Imaging for Dynamic Oxygen Mapping (FREDOM). In addition, BOLD and TOLD MRI measurements were used to predict radiation treatment outcome following a single dose of 30 Gy. BOLD MRI was also assessed in cervical cancer patients in response to breathing oxygen (15dm3/min). Two sequences were tested, multiple-shot EPI and multi echo gradient echo, to allow comparison. Significant correlations were found between BOLD and TOLD MRI and quantitative pO2 measurements for both oxygen and carbogen breathing. However, both gases had similar effect on modulating tumor hypoxia with no significant difference observed. The AT1 tumors showed a correlation between tumor growth delay for the animals breathing O2 during radiation and pre-irradiation TOLD responses to oxygen challenge. Finally, BOLD MRI at 3T was feasible for examining the potentially valuable biomarker of oxygenation seen in cervical cancer. Further parameters such as vascular perfusion and permeability based on DCE, cellularity based on diffusion, and TOLD response to oxygen challenge may also be readily incorporated into a dynamic evaluation.Item Optimization of the Fair Technique for Specific Brain region Perfusion Studies(2009-01-14) Li, Xiufeng; Briggs, Richard W.Most of the technical development and applications of ASL (arterial spin labeling) imaging have mainly focused on the superior cortical regions of the brain. However, optimal ASL measurements to quantify cerebral blood flow (CBF) in specific brain regions may require optimized parameters, improved techniques, or new imaging schemes based upon physiological or anatomic characteristics of those brain regions. In this thesis, the advantages of this region-targeted approach are demonstrated by performing quantitative perfusion studies of two representative brain regions, the cerebellum in the inferior part of the brain and the hippocampus in the mid-brain. To minimize or eliminate the venous artifacts found in cerebellum perfusion studies using traditional FAIR (flow-sensitive alternating inversion recovery) technique, FAIR ASST (FAIR with active suppression of superior tagging technique), as well as MDS FAIR, (modulated dual saturation pulse trains for FAIR) was developed and compared to PICORE (proximal inversion with a control for off-resonance effects) for quantifying cerebellum perfusion. The data indicate that FAIR ASST yields more robust CBF (cerebral blood flow) measurements. OPTIMAL FAIR (orthogonally-positioned tagging imaging method for arterial labeling of FAIR) was developed and shown to reduce the heterogeneity of within-slice transit time and to minimize partial volume effects, improving quantitative CBF maps for cerebellum and hippocampus. These techniques were optimized and applied to the study of perfusion abnormalities in brain regions important to the study of Gulf War Syndrome. Together with regionally optimized parameters, these ASL methods provide more reliable, efficient, accurate, and artifact-free CBF measurements than methods previously available.Item The Use of Ultrasound-Targeted Microbubble Destruction in Mediated Delivery of a Gadolinium Magnetic Resonance Imaging Contrast Agent Into Fibroblast Cells In Vitro(2004-05-04) Russell III, C. Hunter; Sherry, A. DeanA method for delivering Gd-based MRI contrast agents by ultrasound-targeted microbubble destruction into fibroblast cells in vitro is presented. First, MRI contrast agents Gd-F-DOTP-ME and Gd-DOTA-4iBA are shown to associate with liposome microbubbles used as ultrasound contrast agents. Repeated washings with phosphate buffered saline followed by T1 measurements at 20 MHz revealed Gd-DOTA-4iBA was retained more effectively by the liposome microbubbles. Secondly, ultrasound-targeted microbubble destruction using Optison(tm) microbubbles to deliver Gd-DOTA-4iBA into fibroblast cells displays negligible T1 shortening at 4.7T over controls. Further experiments are planned to validate these observations with other MRI contrast agents and other forms of microbubbles used for ultrasound image enhancement. The goal of these experiments is eventually combining MRI contrast agent delivery with ultrasound targeted microbubble destruction gene therapy to quantitatively determine the amount of DNA delivered into target tissues.