Biomedical Research Imaging Center - UNC School of Medicine
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Non-Human Studies
Elizabeth Bullitt, M.D.
Joseph DeSimone, Ph.D.
- Development of ‘Smart’ Nanoparticles for Cancer Therapy and Imaging
- Evaluation of the Applications of ‘Smart’ Nanoparticles to Cancer Therapy and Imaging
Joe Kornegay, DVM, Ph.D.
Weili Lin, Ph.D.
Wenbin Lin, Ph.D. Website
Principal Investigator: Hongyu An, Ph.D.
Brain temperature modulation and MR derived cerebral oxygen metabolic threshold for irreversible ischemic injury
A wealth of evidence has been reported in the literature that hypothermia is neuro-protective and able to minimize neurological injury following ischemic stroke [104-119]. Therefore, the utilization of hypothermia during ischemic insults may prolong the therapeutic window of tPA beyond the currently approved 3hrs to allow more acute stroke patients to receive this treatment. However, the extent to which the therapeutic window can be extended under hypothermia remains unclear given the challenge of how to determine the presence of viable tissues. Using non-human primate ischemic models and positron emission tomography (PET), it has been suggested that cerebral metabolic rate of oxygen (CMRO2) may delineate irreversible injury from viable tissues [93, 94, 120, 121]. The required onsite cyclotron for PET CMRO2 measurement has substantially limited its accessibility. In lieu of PET CMRO2, a measurement referred to as MR cerebral oxygen metabolic index (MR_COMI) has been demonstrated to provide similar physiological information [101, 122]. Based on this established technique, we propose to test whether MR_COMI can be utilized to determine a threshold below which irreversible ischemic injury may occur under normothermia, hypothermia and hyperthermia. To accomplish this goal, an MR compatible device to manipulate brain temperature consistently, accurately, and locally while maintaining a normal core body temperature will be developed. In-vivo brain temperature maps will be obtained by using an MR imaging method. Finally, an MR_COMI threshold below which irreversible ischemic injury may occur under respective normothermic, hypothermic and hyperthermic conditions will be experimentally derived.
Fig. 33 Brain temperature manipulation using the devised developed by our team. Y-axis is temperature in degrees. |
Preliminary results
An MR compatible temperature control device was devised capable of accurately manipulating brain temperature while maintaining a normal core body temperature for a desired period time. As demonstrated in Fig 33 with 5 male long Evan rats (300±25g), five different levels of targeted temperatures (39°C, 37°C, 35°C, 32°C and 29°C) are achieved promptly (< 10 minutes) and maintain for 90-120 minutes with a very small fluctuation (<0.5°C). The rectal temperature remained in the normal range of 37.5°C±0.5°C for all rats.
Fig. 34 T1 (y-axis) vs Temperature (x-axis).
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It has been shown that spin-lattice relaxation time (T1) is linearly proportional to temperature. In this experiment, different brain temperature was induced with our MR compatible temperature manipulation system. T1 maps were obtained using a 3D rf-spoiled gradient echo sequence with five different flip angles. Estimates of T1 obtained from an ROI in a similar location as that of the thermo probe but on the contralateral hemisphere were correlated with the probe readings. A highly linear relationship (y = 6.6937x + 967.36) was observed with an R value of 0.96 (Fig. 34).
Representative publication
Wu Y, An H, Krim H, Lin W. An independent component analysis approach for minimizing effects of recirculation in dynamic susceptibility contrast magnetic resonance imaging. JCBFM, 2007 Mar;27(3):632-45.
H An and W Lin. The impact of intravascular signal on quantitative measures of cerebral oxygen extraction and blood volume under normo and hypercapnic conditions using an asymmetric spin echo approach. MRM, 2003, 50: 708-716.
C.5. Others
C.5.1. Carolina Center of Cancer Nanotechnology Excellence
In 2005, UNC was awarded one of eight NCI Centers of Cancer Nanotechnology Excellence (CCNE). The growing convergence of the physical sciences with biology offers extraordinary biomedical research opportunities. Exciting developments in nanotechnology promise to have a revolutionary impact on basic research and its translation into cancer diagnosis and therapy. The goals of the Carolina CCNE (C-CCNE) are to design and fabricate several types of novel and innovative imaging probes utilizing nanoparticles and nanodevices and to evaluate them in the context of powerful and informative biological models, with the emphasis on mouse tumor models. We believe that this will bring rapid progress in translational research leading to novel diagnostic and therapeutic approaches to cancer. Specifically, the overarching research theme of the CCNE is ‘smart’ nanoparticles. This focus is based on the emergence of a radical new approach to nanoparticle fabrication that was developed at the UNC Chemistry Department. This new nanofabrication technology is being linked to existing local expertise in screening peptide and aptamer combinatorial libraries to generate nanoparticles capable of selective binding to surface receptors on tumor cells or endothelial cells. In addition to nanoparticles, the C-CCNE will also develop several other exciting and novel technologies including carbon nanotube based X-ray sources, nanofluidics based cell analysis, nanopatterned surfaces with unique chemical and optical properties, and magnetic nanoparticles for imaging and therapy of brain tumors. Some of these nanotechnologies are at an advanced stage of development that may lead to clinical evaluation within one to three years. Others are in nascent stages but have the potential to have major impacts on basic or translational cancer research.
Of the six projects proposed in the CCNE, three projects have utilized the Allegra system. Although these are not major users, brief information of the three projects is provided below.
Pricipal Investigator: Elizabeth Bullitt, M.D.
Noninvasive assesment of tumor malignancy
The focus of this study is upon the application of newly developed image processing algorithms to address the basic clinical and biological questions of what happens to tumor-associated vasculature during tumor growth and treatment using state-of-the-art genetically engineered mouse models.
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| Fig 29. Features of GEM-GBM. (a-c) H&E stained sections of GEM-GBM brain with tumor. a: 50X low power shows large frontal mass. b: 400X view shows pseudo palisading necrosis (PPN). c and d are serial sections showing an area of PPN in which surrounding tumor cells express VEGF (d) shown by in situ RNA hybridization. E. Mice develop GBM with consistent TIMing after 4OHT injection as shown in the survival curve (GEM-GBM). Mice in which only T121 was induced survive to old ages with diffuse low grade astrocytoma characteristics. |
Of direct clinical relevance, we aim to evaluate a new method of assessing malignancy and of monitoring tumor treatment response. We also aim to compare this new approach, based upon statistical measures of vessel shape, to the current “best” (but sadly imperfect) methods of non-invasive tumor assessment that use measurements of blood volume, vessel permeability, and tumor volume. On the scientific level, we aim to correlate quantitative measures of vessel tortuosity with physical changes to the vessel wall as seen by histology. The proposed work could provide an important early step toward a better understanding of tumor biology and a better means of monitoring tumor activity noninvasively. The specific aims are
Aim 1: To evaluate the ability of vessel shape analysis as determined from MRA to assess change in tumor grade and to evaluate tumor treatment response in two different, state-of-the-art, genetically engineered mouse brain tumor models.
Aim 2: To examine the correlation of vessel wall abnormalities with quantitative tortuosity measures as determined from MRA, with rCBF measurements, and with vessel permeability.
Justifications for using 3T instead of 9.4T
As mentioned previously, the main imaging method used in this study is high resolution MRA so as to allow the determination of vascular attributes. It is well known that both T1 and T2 depend on the field strength; T1 is increased while T2 is decreased. In the context of MRA, the lengthened T1 of blood will substantially dampen the time-of-flight effects; it takes a longer time for T1 to recover, resulting in T1 saturation in MRA. We have done a comparison of MRA between the two field strengths and results indicate that 3T provides a better vascular visualization when the total acquisition was kept constant between the two field strengths. Therefore, given this major limitation at 9.4T, this study will utilize the 3T MR scanner.
Preliminary results
Two genetically engineered mouse models are employed in which tumors develop spontaneously, with histology identical to that of human tumors, but with tumor development known to appear within a known time frame. One of these models is of choroid plexus carcinoma (CPC; mice develop benign dysplasia at 0-6 weeks of age, solid carcinomas at 6-8 weeks, and tumors large enough to cause death at an average of 12 weeks)[102]. The second is a model of human glioma in which mice are born normal but progressively develop diffuse glioma that proceeds to malignant glioma (grade III) and then, following 4OHT injection, to glioblastoma (grade IV). TgGZT121;K-raslslG12D;Pten+/fl;TgGFAP-CreERTam mice are generated by standard mating schemes and injected with 4OHT at 3 months of age. Four-five months later, animals are moribund with a brain tumor that possesses the hallmark features of human glioblastoma - highly proliferative and invasive tumor cells of variable marker specificities with extensive angiogenesis and the presence of pseudo palisading necrosis (Fig. 29).
Fig. 30-32 illustrate results from a completed study on the evolution of CPC[103]. In this study of evolving carcinomas, vessel shape measures appeared capable of correctly establishing the presence of malignancy once cancers had reached a volume of approximately 1 mm3 or more but could not detect malignancy in tumors smaller than this[103]. This approach thus seems highly promising in detecting even tiny cancers.
Representative Publications:
Bullitt E, Wolthusen PA, Brubaker L, Lin W, Zeng D, Van Dyke T. Malignancy-associated vessel tortuosity: A computer-assisted, mr angiographic study of choroid plexus carcinoma in genetically engineered mice. AJNR Am J Neuroradiol. 2006;27:612-619
Brubaker LM, Bullitt E, Yin C, Van Dyke T, Lin W. Magnetic resonance angiography visualization of abnormal tumor vasculature in genetically engineered mice. Cancer Res. 2005;65:8218-8223
Brubaker LM, Smith JK, Lee YZ, Lin W, Castillo M. Hemodynamic and permeability changes in posterior reversible encephalopathy syndrome measured by dynamic susceptibility perfusion-weighted mr imaging. AJNR Am J Neuroradiol. 2005;26:825-830
Bullitt E, Zeng D, Gerig G, Aylward S, Joshi S, Smith JK, Lin W, Ewend MG. Vessel tortuosity and brain tumor malignancy: A blinded study. Acad Radiol. 2005;12:1232-1240
Principal Investigator: Joseph DeSimone, Ph.D.
Project 1: Development of ‘Smart’ Nanoparticles for Cancer Therapy and Imaging
Project 2: Evaluation of the Applications of ‘Smart’ Nanoparticles to Cancer Therapy and Imaging
The first project focuses on the development, scale-up, and evaluation of ‘smart’ nanoparticles that are produced via a revolutionary new fabrication technology. This project is based on the PRINT (Particle Replication In Non-wetting Templates) technology for nanoparticle fabrication recently developed in the DeSimone laboratory, that essentially “prints” nanoparticles[123]. This process, called “soft” or “non-wetting” imprint lithography, involves first the creation of the desired shape in a silicon template using electron beam lithography techniques adapted from the computer industry. A mold is then made of the template using novel liquid fluoropolymers that can be cured into a Teflon-like solid by polymerization. The mold can then be filled with any desired polymerizable material and the polymerization process initiated. The contents of the mold are then extruded (Fig. 35). PRINT allows one to generate completely isolated nanostructures of virtually any size and shape by taking advantage of the inherently low surface energy and swelling resistance of photocurable perfluoropolyethers (PFPEs).
Nanoparticles fabricated using the PRINT technology are currently under developing as carriers of conventional antitumor drugs, antisense and siRNA oligonucleotides. Specifically, MR contrast agents have been developed and the Allegra has been utilized to characterize the developed contrast agents by measuring both T1 and T2 relaxivities.
Fig. 35 Illustration of PRINT technique. PRINT eliminates the “scum” layer between the features to be molded, enabling the fabrication of free-standing and harvestable particles which have the same precise shape of the master template they were derived from. (DeSimone et al, J Am Chem 2005, 127, 10096. |
The second project is closely linked with the first project listed above and will investigate the utilization nanoparticles fabricated by PRINT technology in cancer diagnosis and therapy. This includes: (1) preparing ‘smart’ nanoparticles linked to cell-targeting peptides or aptamers and studying their interactions with cell targets both in culture and in animals; (2) evaluating the ability of ‘smart’ nanoparticles to deliver drugs or therapeutic oligonucleotides to a variety of mouse tumors and examining the impact on tumor growth; (3) evaluating the ability of ‘smart’ nanoparticles to deliver imaging agents to a variety of mouse tumors. In vivo testing of the nanoparticle based imaging agents has begun. PRINT particles containing commercially available contrast agent OmniscanTM for MR imaging and PRINT particles conjugated to 64Cu, a long-lived positron emitter useful for micro-PET/CT have been fabricated. Enhanced contrast in the kidneys and the blood vessels of the liver is observed using particles containing the contrast agent OmniscanTM (Fig 36). Biodistribution of PEG-based hydrogels conjugated to 64Cu have also been conducted in collaboration with Phelps at UCLA. Similar to the results observed for the biodistribution study using 125I as the radiotracer, the PET images suggest a relatively short half-life with most of the particles sequestered in the liver.
Figure 36. Contrast observed in the kidneys
45 minutes after injection of contrast agent
loaded PRINT nanoparticles.
Principal Investigator: Joe Kornegay, DVM, Ph.D.
Proposal for Establishment of the National Center for Canine Models of
Duchenne Muscular Dystrophy (NCDMD)
Aim 1. Establish infrastructure and organization components of the NCDMD, including:
(a) Administrative and Quality Coordination Office (AQCO), which will conduct and manage day-to-day aspects of the primary CMDF and corresponding service facilities and oversee each facility’s quality control program.
(b) A Steering Committee, which will oversee issues pertaining to program selection, program management, program milestones and advancement, intellectual property, public dissemination of data as well as refining and adapting NCDMD strategies in response to possible changing definitions of “best practices.”
(c) An Operations Committee, which will manage day-to-day activities of the NCDMD. This committee will work in tandem with the Steering Committee to set policies of the NCDMD and its cores, to include development of needed procedures and fees to be charged. Most importantly, the Operations Committee will meet monthly to review progress of ongoing projects conducted through the NCDMD.
(d) A Canine Muscular Dystrophy Facility(CMDF), which will produce and maintain a breeding colony of well-characterized dogs with genetically-determined muscular dystrophy.
(e) Service facilities including the Physiology Testing Facility (PTF), Histology & Molecular Services Facility (H&MSF) and Large Animal Imaging Facility (LAIF), which will provide specialized support services for research projects using the dogs bred and maintained at the CMDF
Aim 2. Conduct translational research focused on therapeutic strategies for DMD
Preliminary results and updates
Pilot imaging studies were conducted using the Allegra system and exciting results have been obtained. Fig. 39 shows a comparison between a control and a DMD dogs. Notice the increased fat content in the DMD dog. While we are pleased with the preliminary results, one of the potential difficulties for the Allegra system is the inability to image older/larger dogs. In particular, the golden retriever muscular dystrophy (GRMD) model will be employed for the proposed studies which can be difficult to fit into the head coil when they become adults (90lbs). Therefore, a whole body MR scanner will be desperately needed for the success of this application. This application is currently under review and we should hear back in the very near future.
Fig 37: Structural MRI of the proximal pelvic limb from control beagle (left) and GRMD dog (right). Overall, higher fat content is visible in the GRMD dog vs. control in all images. |
Principal Investigator: Weili Lin, Ph.D.
MR Measured Oxygen Metabolic Index in Ischemic Stroke
Several lines of evidence derived from positron emission tomography (PET) studies suggest that measures of cerebral metabolic rate of oxygen utilization (CMRO2) provide an indication of brain tissue viability during cerebral ischemia[93-97]. Although PET is a currently available technology to measure CMRO2, the need for an onsite cyclotron has limited its availability to only a few medical centers. Therefore, alternative approaches capable of providing similar physiological information as that of PET CMRO2 could have profound clinical implications. Towards this end, we have recently developed an MR imaging approach capable of measuring cerebral oxygen metabolic activity, which we have termed MR cerebral oxygen metabolic index (MR_COMI)[98-101]. Although physically different from PET CMRO2, preliminary results based on MR_COMI are encouraging, suggesting that this approach may indeed reveal similar physiological information as that of PET CMRO2. However, in order to determine if MR_COMI can delineate tissue viability during ischemia, a direct comparison between MR_COMI predicted tissue infarction and final tissue outcome under experimental conditions that are highly clinically relevant is of paramount importance. Therefore, specific aims for this study are
Aim 1: To experimentally derive an MR_COMI threshold below which tissue becomes irreversibly injured and to determine that this MR_COMI threshold is capable of assessing temporal and spatial evolution of ischemic lesions.
Aim 2: To empirically determine the predictive value of this MR_COMI threshold value under a variety of clinically relevant experimental conditions that are known to alter infarct volume and to determine if this MR_COMI threshold is time-independent.
Experiment 2a: Effect of genetic background
Experiment 2b: Effect of body temperature
Experiment 2c: Effect of ischemia model and treatment
Aim 3: To determine how cerebral ischemia induces alteration of cerebral Hct (cHct) using a SPECT approach.
Justification for using the 3T instead of the 9.4T
The underlying concepts of the proposed approaches to obtain quantitative measures of MR_COMI are largely based on the local susceptibility induced by the presence of deoxyhemoglobin. In this context, it is clear that the 9.4T scanner will be a better choice than the 3T since susceptibility effects will be enhanced at 9.4T which in turn improve the sensitivity of the proposed methods. While it is tempting to conduct our studies at 9.4T, one of the major focuses as well as suggestions from reviewers is to rapidly apply the proposed methods into clinical arena upon the completion of the proposed experimental validation. To this end, if we had conducted our studies at 9.4T, we would need to repeat our experiments at 3T prior to conducting clinical studies. Therefore, this study will remain at 3T despite the availability of a 9.4T scanner at our institution.
Preliminary results
Fig. 26 MR venous cerebral blood oxygenation under different experimental conditions, including hypoxia and hypercapnia. The color bar represents blood oxygenation |
One rat undergoing control, mild hypoxia, control and severe hypoxia and another rat undergoing hypercapnia are shown in Fig. 26, demonstrating that the approach developed in this study is capable of discerning changes of cerebral blood oxygenation in response to experimental conditions. Consistent with the anticipated cerebral hemodynamic responses to hypoxia and hypercapnia, a mild reduction and severe reduction of cerebral blood oxygenation are observed under the two hypoxic conditions, respectively, while an increase of cerebral blood oxygenation is observed during hypercapnia. In addition, the cerebral blood oxygenation is similar between the two control states, demonstrating the stability of the proposed approaches.
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Here we will provide preliminary results on the temporal evolution of MR_COMI in rats (n=20) undergoing 90 min MCAO. MR_OEFI and DWI were obtained every 15 min throughout the entire MCAO episode. CBF was obtained at 90 min post-MCAO using the dynamic susceptibility approach. Since an intraluminal suture middle cerebral artery occlusion (MCAO) was used in this study, CBF should remain stable for the entire 90 min imaging session. Immediately after the imaging session, the suture was withdrawn from the MCA to restore CBF for reperfusion. A T2-weighted sequence was used to acquire images 24 hours after MCAO. All of the acquired images were rigidly co-registered (both acute and chronic) using FSL 3.2 (FMRIB, Oxford, UK). Final T2 lesion was defined as the hyper-intense regions (greater than mean + 2 * standard deviation of the signal intensity in the contralateral hemisphere) in the co-registered 24-hour T2W images.
Representative examples from five rats (rows a-e) with different degrees of ischemic injuries are shown in Fig. 27. Temporal evolution of MR_COMI, CBF at 90 min, and 24hrs T2-weighted images are shown for each rat. Using the size of the T2 lesion as a gauge for ischemic severity, the severity progressively decreases from rows a to c and rows d-e have no visible T2 lesions. In row a, MR_COMI is markedly reduced immediately after MCAO and throughout the entire ischemic duration, suggesting that the brain tissue is severely injured immediately after MCAO onset. The region with a substantial reduction of MR_COMI observed at 75min after MCAO is similar to the final T2 lesion (24hrs). In contrast, although a large region of mild MR_COMI reduction is observed in row b, only a small region with a severe reduction of MR_COMI is observed immediately after MCAO (arrow) and this region continues to evolve as a function time (arrow). The temporal characteristics of MR_COMI in row c are similar to that in row b; the region with severely diminished MR_COMI is initially small and continues to evolve as a function of time. Nevertheless, the final T2 lesion is much smaller when compared with that in rows a and b, demonstrating the spatial sensitivity of the proposed method. Finally, while the intraluminal suture was in place as evidence on the 90 min CBF maps in rows d and e where a slight reduction in CBF is present, no T2 lesion is observed for rats in rows d and e. In both cases, only a slight reduction of MR_COMI is observed in both rats. These results demonstrate that the proposed approach for obtaining MR_COMI is highly effective in delineating a different degree of ischemic injuries.
To further investigate the temporal behavior of the distribution of MR_COMI values in the T2/CBF matched region, a histogram analysis was employed for all 20 rats. For the clarity of presentation, we only show the averaged histograms at 0-15 min, 30-45min, and 75-90min after MCAO in Fig. 28. In addition, the histogram obtained from the peri-lesion region at 75-90min after MCAO is also shown for comparison (Peri in Fig. 28). Several important conclusions can be drawn from these histograms. First, the corresponding normalized MR_COMI values of the peaks of the three histograms in the matched T2/CBF ROI appear to be independent of the ischemia duration, suggesting that the mean MR_COMI is stable throughout the entire MCAO duration. This finding is consistent with Fig. 27. Second, the shoulder (solid arrow) for the 0-15 min histogram becomes less apparent and appears shift left in the 30-45min histogram, suggesting that more pixels evolve from a higher to lower MR_COMI. This behavior is even more apparent for the 75-90min histogram (dashed arrow). Finally, the histograms between the T2/CBF matched and peri-lesion regions are well separated, further supporting the notion that experimentally determining an MR_COMI threshold for irreversible injury is highly feasible.
Fig. 28 Histogram analysis of the T2/CBF matched regions at three different times during MCAO along with the histogram of the T2/CBF mismatched region (Peri). |
Representative publications:
Wu Y, An H, Krim H, Lin W. An independent component analysis approach for minimizing effects of recirculation in dynamic susceptibility contrast magnetic resonance imaging. JCBFM, 2007 Mar;27(3):632-45.
H An and W Lin. The impact of intravascular signal on quantitative measures of cerebral oxygen extraction and blood volume under normo and hypercapnic conditions using an asymmetric spin echo approach. MRM, 2003, 50: 708-716.
KD Vo, W Lin, JM Lee. Evidence-based neuroimaging in acute ischemic stroke. Neuroimaging clinics of North America, 2003, 13:167-183.
W Lin, JM Lee, YZ Lee, KD Vo, T Pilgram, CY Hsu Temporal Relationship Between Apparent Diffusion Coefficient and Absolute Measurements of Cerebral Blood Flow in Acute Stroke Patients, Stroke 2003 34: 64 - 70.
JM Lee, KD Vo, H An, A Celik, Y Lee, CY. Hsu, W Lin. Cerebral Metabolic Rate of Oxygen Utilization in Hyperacute Stroke Patients. Annals of Neurology, 2003, 53:227-232.
Principal Investigator: Wenbin Lin, Ph.D.
Brain Tumor Imaging and Therapy using Magnetic Nanoparticles
Glioblastomas are a particularly intractable form of cancer and new approaches to diagnosis and therapy are sorely needed. This project addresses that need by building on innovative magnetic nanoparticle fabrication technology recently developed in Dr. Lin’s laboratory and on new murine brain tumor models developed by Dr. Van Dyke. The iron-oxide and gadolinium-based nanoparticles fabricated by Dr. Lin can be made extremely small (less than 20nm) and thus have the potential to escape the vasculature and enter tumors. Their surfaces can also be manipulated so as to achieve long circulation lifetimes and they can be linked to cell targeting peptides or aptamers. Since they are magnetic, these particles can be manipulated in vivo through the application of external magnetic fields using technology provided by Dr. R. Superfine of the Dept. of Physics.
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In the first Aim Dr. Lin will prepare a variety of magnetic nanoparticles differing in size, surface characteristics, and the presence of targeting moieties. In some cases these particles will also contain MRI contrast agents. The physical characteristics of the nanoparticles and their stability in physiological fluids will be examined. In the second Aim, means for manipulating the biodistribution and functions of several types of magnetic nanoparticles will be developed. In the third Aim these approaches will be applied to imaging and therapy of brain tumors in a murine model. Of particular interest will be the deposition of the nanoparticles within mouse brain tumors as monitored by MRI. The third Aim will also deal with therapeutic applications. Thus magnetic nanoparticles will be developed that preferentially deposit within the brain tumors after systemic administration.
Preliminary results using a reverse microemulsion synthetic methodology recently developed in Dr. Wenbin Lin’s lab for the synthesis of these new multimodal contrast agents are shown in Fig. 36. These nanospheres exhibit an R1 relaxivity of 19.7 s-1 per mM of Gd3+ (~4×105 s-1 per mM of nanosphere) and an R2 relaxivity of 60.0 s-1 per mM Gd3+ (~1.2×106 s-1 per mM of nanosphere) measured on the 3T scanner. The nanospheres have also been labeled with a range of inorganic and organic fluorophores that emit in a diverse range of wavelengths. Such optical labeling greatly facilitates the in vitro studies of the interactions between the nanospheres and desired cells as well as determination of biodistribution of the nanospheres after in vivo imaging studies.
Summary for CCNE related projects
The overall MR scanner usage for all three projects was 25.25 hrs during FY07. However, as these projects continue to develop novel MR contrast agents and the need to characterize these contrast agents in an in vivo environment, it is anticipated that the usage for these projects will be increased to ~60 hrs during FY08. One may wonder why not use the 9.4T MR scanner for these projects. This is due to the fact that one of the major emphases of CCNE is to rapidly translate the developed agents into clinical domain. As a result, characterizing these developed agents needs to be done on a clinically available field strength.
C.5.2. Pilot Studies Supported by the Biomedical Research Imaging Center
As mentioned previously, the BRIC had issued an RFA previously and has funded 5 projects focusing on imaging research. Here we provide brief descriptions of the projects that utilize the 3T MR scanner and will summarize the total usage of these projects during FY2007. Please note that a new RFA will soon be issued by the BRIC. Therefore, we expect that the demands for MR scanner time should remain similar as that during FY07 for the new BRIC pilot studies.