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Challenges and Approaches to Quantitative Therapy Response Assessment in Glioblastoma Multiforme Using the Novel Apoptosis Positron Emission Tomography Tracer F-18 ML-10
Oborski, Matthew J; Laymon, Charles M; Qian, Yongxian; Lieberman, Frank S; Nelson, Arden D; Mountz, James M
Evaluation of cancer-therapy efficacy at early time points is necessary for realizing the goal of delivering maximally effective treatment. Molecular imaging with carefully selected tracers and methodologies can provide the means for realizing this ability. Many therapies are aimed at inducing apoptosis in malignant tissue; thus, the ability to quantify apoptosis in vivo may be a fruitful approach. Apoptosis rate changes occur on a fast time scale, potentially allowing correspondingly rapid decisions regarding therapy value. However, quantification of tissue status based on apoptosis imaging is complicated by this time scale and by the spatial heterogeneity of the process. Using the positron emission tomography (PET) tracer 2-(5-fluoro-pentyl)-2-methyl-malonic acid (F-18 ML-10), we present methods of voxelwise analysis yielding quantitative measures of apoptosis changes, parametric apoptosis change images, and graphical representation of apoptotic features. A method of deformable registration to account for anatomic changes between scan time points is also demonstrated. Overall apoptotic rates deduced from imaging depend on tumor density and the specific rate of apoptosis, a situation resulting in an ambiguity in the source of observed image-based changes. The ambiguity may be resolved through multimodality imaging. An example of intracellular sodium magnetic resonance imaging coupled with F-18 ML-10 PET is provided.
PMCID:3998694
PMID: 24772214
ISSN: 1936-5233
CID: 4968472
Superparamagnetic iron oxide is suitable to label tendon stem cells and track them in vivo with MR imaging
Yang, Yunfa; Zhang, Jianying; Qian, Yongxian; Dong, Shiwu; Huang, He; Boada, Fernando E; Fu, Freddie H; Wang, James H-C
Tendon stem cells (TSCs) may be used to effectively repair or regenerate injured tendons. However, the fates of TSCs once implanted in vivo remain unclear. This study was aimed to determine the feasibility of labeling TSCs with super-paramagnetic iron oxide (SPIO) nano-particles to track TSCs in vivo using MRI. Rabbit TSCs were labeled by incubation with 50 mug/mL SPIO. Labeling efficiency, cell viability, and proliferation were then measured, and the stemness of TSCs was tested by quantitative real time RT-PCR (qRT-PCR) and immunocytochemistry. We found that the labeling efficiency of TSCs reached as high as 98%, and that labeling at 50 mug/mL SPIO concentrations did not alter cell viability and cell proliferation compared to non-labeled control cells. Moreover, the expression levels of stem cell markers (Nucleostemin, Nanog, and Oct-4) did not change in SPIO-labeled TSCs compared to non-labeled cells. Both labeled and non-labeled cells also exhibited similar differentiation potential. Finally, labeled TSCs could be detected by MRI both in vitro and in vivo. Taken together, the findings of this study show that labeling TSCs with SPIO particles is a feasible approach to track TSCs in vivo by MRI, which offers a non-invasive method to monitor repair of injured tendons.
PMCID:3766440
PMID: 23549900
ISSN: 0090-6964
CID: 910382
Repeatability of ultrashort echo time-based two-component T2* measurements on cartilages in human knee at 3 T
Qian, Yongxian; Williams, Ashley A; Chu, Constance R; Boada, Fernando E
Repeatability of in vivo measurement of multicomponent T2* relaxation in articular cartialges in human knee is important to clinical use. This study evaluated the repeatability of two-component T2* relaxation on seven healthy human subjects. The left knee was scanned once a day in three consecutive days, on a clinical 3T MRI scanner with eight-channel knee coil and ultrashort echo time pulse sequence at 11 echo times=0.6-40 ms. The intrasubject and intersubject repeatability was evaluated via coefficient of variation (CV=standard deviation/mean) in four typical cartilage regions: patellar, anterior articular, femoral, and tibial regions. It was found that the intrasubject repeatability was good, with CV<10% for the short- and long-T2* relaxation time in the layered regions in the four cartilages (with one exception) and CV<13% for the component intensity fraction (with two exceptions). The intersubject repeatability was also good, with CV approximately 8% (range 1-15%) for the short- and long-T2* relaxation time and CV approximately 10% (range 2-20%) for the component intensity fraction. The long-T2* component showed significantly better repeatability (CV approximately 8%) than the short-T2* component (CV approximately 12%) (P<0.005). These CV values suggest that in vivo measurement of two-component T2* relaxation in the knee cartilages is repeatable on clinical scanner at 3 T, with a signal-to-noise ratio of 90.
PMCID:3538116
PMID: 23034822
ISSN: 0740-3194
CID: 910352
Multi-slice parallel transmission three-dimensional tailored RF (PTX 3DTRF) pulse design for signal recovery in ultra high field functional MRI
Zheng, Hai; Zhao, Tiejun; Qian, Yongxian; Schirda, Claudiu; Ibrahim, Tamer S; Boada, Fernando E
T(2)( *) weighted fMRI at high and ultra high field (UHF) is often hampered by susceptibility-induced, through-plane, signal loss. Three-dimensional tailored RF (3DTRF) pulses have been shown to be an effective approach for mitigating through-plane signal loss at UHF. However, the required RF pulse lengths are too long for practical applications. Recently, parallel transmission (PTX) has emerged as a very effective means for shortening the RF pulse duration for 3DTRF without sacrificing the excitation performance. In this article, we demonstrate a RF pulse design strategy for 3DTRF based on the use of multi-slice PTX 3DTRF to simultaneously and precisely recover signal with whole-brain coverage. Phantom and human experiments are used to demonstrate the effectiveness and robustness of the proposed method on three subjects using an eight-channel whole body parallel transmission system.
PMCID:3581716
PMID: 23348046
ISSN: 1090-7807
CID: 910372
Sodium imaging of human brain at 7 T with 15-channel array coil
Qian, Yongxian; Zhao, Tiejun; Wiggins, Graham C; Wald, Lawrence L; Zheng, Hai; Weimer, Jonathan; Boada, Fernando E
Signal-to-noise ratio (SNR) is a major challenge to sodium magnetic resonance imaging. Phased array coils have been shown significantly improving SNR in proton imaging over volume coils. This study investigates SNR advantage of a 15-channel array head coil (birdcage volume coil for transmit/receive and 15-channel array insert for receive-only) in sodium imaging at 7 T. Phantoms and healthy human brains were scanned on a whole-body 7 T magnetic resonance imaging scanner using a customer-developed pulse sequence with the twisted projection imaging trajectory. Noise-only images were acquired with blanked radiofrequency excitations for noise measurement on a pixel basis. SNR was calculated on the root of sum-of-squares images. When compared with the volume coil, the 15-channel array produced SNR more than doubled at the periphery and slightly increased at the center of the phantoms and human brains. Decorrelation of noise across channels of the array coil extended the SNR-doubled region into deep area of the brain. The spatial modulation of element sensitivities on the sum-of-squares combined image was removed by performing self-calibrated sensitivity encoding parallel image reconstruction and uniform image intensity across entire field of view was attained. The 15-channel array coil is an efficient tool to substantially improve SNR in sodium imaging on human brain. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc.
PMID: 22377960
ISSN: 0740-3194
CID: 175943
Parallel transmission RF pulse design for eddy current correction at ultra high field
Zheng, Hai; Zhao, Tiejun; Qian, Yongxian; Ibrahim, Tamer; Boada, Fernando
Multidimensional spatially selective RF pulses have been used in MRI applications such as B(1) and B(0) inhomogeneities mitigation. However, the long pulse duration has limited their practical applications. Recently, theoretical and experimental studies have shown that parallel transmission can effectively shorten pulse duration without sacrificing the quality of the excitation pattern. Nonetheless, parallel transmission with accelerated pulses can be severely impeded by hardware and/or system imperfections. One of such imperfections is the effect of the eddy current field. In this paper, we first show the effects of the eddy current field on the excitation pattern and then report an RF pulse the design method to correct eddy current fields caused by the RF coil and the gradient system. Experimental results on a 7T human eight-channel parallel transmit system show substantial improvements on excitation patterns with the use of eddy current correction. Moreover, the proposed model-based correction method not only demonstrates comparable excitation patterns as the trajectory measurement method, but also significantly improves time efficiency.
PMCID:3418061
PMID: 22789452
ISSN: 1090-7807
CID: 175936
High-resolution sodium imaging of human brain at 7 T
Qian, Yongxian; Zhao, Tiejun; Zheng, Hai; Weimer, Jonathan; Boada, Fernando E
The feasibility of high-resolution sodium magnetic resonance imaging on human brain at 7 T was demonstrated in this study. A three-dimensional anisotropic resolution data acquisition was used to address the challenge of low signal-to-noise ratio associated with high resolution. Ultrashort echo-time sequence was used for the anisotropic data acquisition. Phantoms and healthy human brains were studied on a whole-body 7-T magnetic resonance imaging scanner. Sodium images were obtained at two high nominal in-plane resolutions (1.72 and 0.86 mm) at a slice thickness of 4 mm. Signal-to-noise ratio in the brain image (cerebrospinal fluid) was measured as 14.4 and 6.8 at the two high resolutions, respectively. The actual in-plane resolution was measured as 2.9 and 1.6 mm, 69-86% larger than their nominal values. The quantification of sodium concentration on the phantom and brain images enabled better accuracy at the high nominal resolutions than at the low nominal resolution of 3.44 mm (measured resolution 5.5 mm) due to the improvement of in-plane resolution.
PMCID:3297679
PMID: 22144258
ISSN: 0740-3194
CID: 175940
Sodium MRI and the assessment of irreversible tissue damage during hyper-acute stroke
Boada, Fernando E; Qian, Yongxian; Nemoto, Edwin; Jovin, Tudor; Jungreis, Charles; Jones, S C; Weimer, Jonathan; Lee, Vincent
Sodium MRI (sMRI) has undergone a tremendous amount of technical development during the last two decades that makes it a suitable tool for the study of human pathology in the acute setting within the constraints of a clinical environment. The salient role of the sodium ion during impaired ATP production during the course of brain ischemia makes sMRI an ideal tool for the study of ischemic tissue viability during stroke. In this paper, the current limitations of conventional MRI for the determination of tissue viability during evolving brain ischemia are discussed. This discussion is followed by a summary of the known findings about the dynamics of tissue sodium changes during brain ischemia. A mechanistic model for the explanation of these findings is presented together with the technical requirements for its investigation using clinical MRI scanners. An illustration of the salient features of the technique is also presented using a nonhuman primate model of reversible middle cerebral artery occlusion.
PMID: 24323779
ISSN: 1868-4483
CID: 910412
High-resolution ultrashort echo time (UTE) imaging on human knee with AWSOS sequence at 3.0 T
Qian, Yongxian; Williams, Ashley A; Chu, Constance R; Boada, Fernando E
PURPOSE: To demonstrate the technical feasibility of high-resolution (0.28-0.14 mm) ultrashort echo time (UTE) imaging on human knee at 3T with the acquisition-weighted stack of spirals (AWSOS) sequence. MATERIALS AND METHODS: Nine human subjects were scanned on a 3T MRI scanner with an 8-channel knee coil using the AWSOS sequence and isocenter positioning plus manual shimming. RESULTS: High-resolution UTE images were obtained on the subject knees at TE = 0.6 msec with total acquisition time of 5.12 minutes for 60 slices at an in-plane resolution of 0.28 mm and 10.24 minutes for 40 slices at an in-plane resolution of 0.14 mm. Isocenter positioning, manual shimming, and the 8-channel array coil helped minimize image distortion and achieve high signal-to-noise ratio (SNR). CONCLUSION: It is technically feasible on a clinical 3T MRI scanner to perform UTE imaging on human knee at very high spatial resolutions (0.28-0.14 mm) within reasonable scan time (5-10 min) using the AWSOS sequence.
PMCID:5823004
PMID: 22002811
ISSN: 1053-1807
CID: 175945
Improved large tip angle parallel transmission pulse design through a perturbation analysis of the Bloch equation
Zheng, Hai; Zhao, Tiejun; Qian, Yongxian; Ibrahim, Tamer S; Boada, Fernando E
Parallel transmission has emerged as an efficient means for implementing multidimensional spatially selective radiofrequency excitation pulses. To date, most theoretical and experimental work on parallel transmission radiofrequency (RF) pulse design is based on the small-tip-angle approximation to the Bloch equation. The small-tip-angle, while mathematically compact, is not an exact solution and leads to significant errors when large-tip-angle pulses are designed. Methods have been proposed to overcome the limitations of the small-tip-angle using regularized least-square optimization or optimal control algorithms. These methods, however, are based on further approximations to the Bloch equation or require the use of general purpose algorithms that do not capitalize fully on the dynamics of the physical model at hand. In this article, a novel algorithm for large-tip-angle parallel transmission pulse design is proposed. The algorithm relies on a perturbation analysis of the Bloch equation and it depicts the relationship between the excited magnetization, its deviation from the target pattern and the desired pulses. Simulations and experiments are used to validate the proposed method on a 7 T 8-channel transmit array. The results demonstrate that the perturbation analysis algorithm provides a fast and accurate approach for multidimensional large-tip-angle pulse design, especially when large acceleration factors and/or echo-planar trajectories are used.
PMCID:3156310
PMID: 21520270
ISSN: 0740-3194
CID: 175946