Faculty Bibliography

We evaluate novel magnetic resonance imaging (MRI) and positron emission tomography (PET) quantitative imaging biomarkers and associated multimodality, serial-time-point analysis methodologies, with the ultimate aim of providing clinically feasible, predictive measures for early assessment of response to cancer therapy. A focus of this work is method development and an investigation of the relationship between the information content of the two modalities. Imaging studies were conducted on subjects who were enrolled in glioblastoma multiforme (GBM) therapeutic clinical trials. Data were acquired, analyzed and displayed using methods that could be adapted for clinical use. Subjects underwent dynamic [(18)F]fluorothymidine (F-18 FLT) PET, sodium ((23)Na) MRI and 3-T structural MRI scans at baseline (before initiation of therapy), at an early time point after beginning therapy and at a late follow-up time point after therapy. Sodium MRI and F-18 FLT PET images were registered to the structural MRI. F-18 FLT PET tracer distribution volumes and sodium MRI concentrations were calculated on a voxel-wise basis to address the heterogeneity of tumor physiology. Changes in, and differences between, these quantities as a function of scan timing were tracked. While both modalities independently show a change in tissue status as a function of scan time point, results illustrate that the two modalities may provide complementary information regarding tumor progression and response. Additionally, tumor status changes were found to vary in different regions of tumor. The degree to which these methods are useful for GBM therapy response assessment and particularly for differentiating true progression from pseudoprogression requires additional patient data and correlation of these imaging biomarker changes with clinical outcome.

INTRODUCTION: The National Cancer Institute Quantitative Research Network (QIN) is a collaborative research network whose goal is to share data, algorithms and research tools to accelerate quantitative imaging research. A challenge is the variability in tools and analysis platforms used in quantitative imaging. Our goal was to understand the extent of this variation and to develop an approach to enable sharing data and to promote reuse of quantitative imaging data in the community. METHODS: We performed a survey of the current tools in use by the QIN member sites for representation and storage of their QIN research data including images, image meta-data and clinical data. We identified existing systems and standards for data sharing and their gaps for the QIN use case. We then proposed a system architecture to enable data sharing and collaborative experimentation within the QIN. RESULTS: There are a variety of tools currently used by each QIN institution. We developed a general information system architecture to support the QIN goals. We also describe the remaining architecture gaps we are developing to enable members to share research images and image meta-data across the network. CONCLUSIONS: As a research network, the QIN will stimulate quantitative imaging research by pooling data, algorithms and research tools. However, there are gaps in current functional requirements that will need to be met by future informatics development. Special attention must be given to the technical requirements needed to translate these methods into the clinical research workflow to enable validation and qualification of these novel imaging biomarkers.

Alternate ascending/descending directional navigation (ALADDIN) is a new imaging technique that provides interslice perfusion-weighted and magnetization transfer (MT) asymmetry images. In this article, we investigated the effects of gradient imperfections on ALADDIN MT asymmetry (MTA) signals. Subtraction artifacts increasing with readout offsets were detectable in ALADDIN MTA images from an agarose phantom but not from a water phantom. Slice-select offsets had no significant effect on the artifacts in MTA. The artifacts were suppressed by averaging signals over the readout gradient polarities independent of scan parameters. All these results suggested that the subtraction artifacts were induced by readout eddy currents. With suppression of the artifacts, ALADDIN signals in human brain and skeletal muscle varied less with scan conditions. Percent signal changes of MTA in human skeletal muscle (0.51 +/- 0.11%, N = 3) were about 30% of those in white matter. The new averaging scheme will allow for more accurate MTA imaging with ALADDIN, especially at off-center positions. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc.

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.

BACKGROUND: : High-definition fiber tracking (HDFT) is a novel combination of processing, reconstruction, and tractography methods that can track white matter fibers from cortex, through complex fiber crossings, to cortical and subcortical targets with subvoxel resolution. OBJECTIVE: : To perform neuroanatomical validation of HDFT and to investigate its neurosurgical applications. METHODS: : Six neurologically healthy adults and 36 patients with brain lesions were studied. Diffusion spectrum imaging data were reconstructed with a Generalized Q-Ball Imaging approach. Fiber dissection studies were performed in 20 human brains, and selected dissection results were compared with tractography. RESULTS: : HDFT provides accurate replication of known neuroanatomical features such as the gyral and sulcal folding patterns, the characteristic shape of the claustrum, the segmentation of the thalamic nuclei, the decussation of the superior cerebellar peduncle, the multiple fiber crossing at the centrum semiovale, the complex angulation of the optic radiations, the terminal arborization of the arcuate tract, and the cortical segmentation of the dorsal Broca area. From a clinical perspective, we show that HDFT provides accurate structural connectivity studies in patients with intracerebral lesions, allowing qualitative and quantitative white matter damage assessment, aiding in understanding lesional patterns of white matter structural injury, and facilitating innovative neurosurgical applications. High-grade gliomas produce significant disruption of fibers, and low-grade gliomas cause fiber displacement. Cavernomas cause both displacement and disruption of fibers. CONCLUSION: : Our HDFT approach provides an accurate reconstruction of white matter fiber tracts with unprecedented detail in both the normal and pathological human brain. Further studies to validate the clinical findings are needed. ABBREVIATIONS: : DSI, diffusion spectrum imagingDTI, diffusion tensor imagingHDFT, high-definition fiber tractography.

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.

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.

For patients with traumatic brain injury (TBI), current clinical imaging methods generally do not provide highly detailed information about the location of axonal injury, severity of injury, or expected recovery. In a case of severe TBI, the authors applied a novel high-definition fiber tracking (HDFT) to directly visualize and quantify the degree of axonal fiber damage and predict functional deficits due to traumatic axonal injury and loss of cortical projections. This 32-year-old man sustained a severe TBI. Computed tomography and MRI revealed an area of hemorrhage in the basal ganglia with mass effect, but no specific information on the location of axonal injury could be obtained from these studies. Examinations of the patient at Week 3 and Week 8 after TBI revealed motor weaknesses of the left extremities. Four months postinjury, 257-direction diffusion spectrum imaging and HDFT analysis was performed to evaluate the degree of axonal damage in the motor pathway and quantify asymmetries in the left and right axonal pathways. High-definition fiber tracking was used to follow corticospinal and corona radiata pathways from the cortical surface to the midbrain and quantify projections from motor areas. Axonal damage was then localized by assessing the number of descending fibers at the level of the cortex, internal capsule, and midbrain. The motor deficit apparent in the clinical examinations correlated with the axonal losses visualized using HDFT. Fiber loss estimates at 4 months postinjury accurately predicted the nature of the motor deficits (severe, focal left-hand weakness) when other standard clinical imaging modalities did not. A repeat scan at 10 months postinjury, when edema and hemorrhage had receded, replicated the fiber loss. Using HDFT, the authors accurately identified the presence and location of damage to the underlying white matter in this patient with TBI. Detailed information of injury provided by this novel technique holds future potential for precise neuroimaging assessment of TBI.

OBJECTIVES: We investigated the accuracy of high-field proton magnetic resonance spectroscopy ((1) H MRS) and fluorine-18 2-fluoro-deoxyglucose positron emission tomography ((18) F-FDG-PET) for diagnosis of glioma progression following tumor resection, stereotactic radiation, and chemotherapy. METHODS: Twelve post-therapy patients with histology proven gliomas (six grade II and six grade III) presented with magnetic resonance imaging (MRI) and clinical symptoms suggestive but not conclusive of progression were entered into the study. (1) H MRS data were acquired and 3-dimensional volumetric maps of choline (Cho) over creatine (Cr) were generated. Intensity of (18) F-FDG uptake was evaluated on a semiquantitative scale. RESULTS: The accuracy of (1) H MRS and (18) F-FDG-PET imaging for diagnosis of glioma progression was 75% and 83%, respectively. Classifying the tumors by grade improved accuracy of (18) F-FDG-PET to 100% in high-grade gliomas and accuracy of (1) H MRS to 80% in low-grade tumors. Spearman's analysis demonstrated a trend between (18) F-FDG uptake and tumor grading (rho= .612, P-value = .272). The results of (18) F-FDG-PET and (1) H MRS were concordant in 75% (9/12) of cases. CONCLUSION: The combination of (1) H MRS data and (18) F-FDG-PET imaging can enhance detection of glioma progression. (1) H MRS imaging was more accurate in low-grade gliomas and (18) F-FDG-PET provided better accuracy in high-grade gliomas.

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.