Phantom study evaluating detection of simulated upper airway occlusion using piezoelectric ultrasound transducers.

Obstructive sleep apnea/hypopnea syndrome (OSAHS) is characterized by repetitive narrowing or full collapse of the upper airway concomitant with continued respiratory effort during sleep lasting 10s or more. OSAHS is the most prevalent form of sleep-disordered breathing, affecting more than 17% of the middle-aged U.S. POPULATION: Hence, many individuals need to be tested for having OSAHS. Currently, detection of airway occlusion due to OSAHS is achieved by indirect measurements, often requiring multiple sensor types, such as a flow transducer combined with chest and abdomen plethysmography. The need for the use of multiple sensors in the current OSAHS detection systems adds to the cost and complexity of the current systems and associated procedures. Development of a simple sensor system that allows direct detection of airway occlusion is advantageous, as it simplifies detection of OSAHS and paves the way for home diagnosis of OSAHS. The utilization of ultrasonic transducers is attractive, as it is non-invasive and non-ionizing. We present a new ultrasound sensing system for direct detection of the occlusion in the upper airway in OSAHS patients during sleep. The system takes into consideration the constraints arising from the location of probing and the acoustic requirements for transducers. The physiological and theoretical backgrounds are presented for using ultrasonic pulses to detect the presence and degree of occlusion in the airway. The proposed methodology for creating an anthropomorphically-correct neck and airway phantoms to test the hypothesis and the results of the tests are presented. HYPOTHESIS: An ultrasonic signal transmitted through or reflected from an open airway will have different features compared to those associated with a partially or fully occluded airway. METHODOLOGY: A system, comprising a phantom model of the airway and neck with the approximate anatomical-correct dimensions and acoustic properties of the airway, is designed and built. It allows simulating fully open airway as well as hypopnea and apnea events. Further, it facilitates probing using multiple ultrasonic frequencies and transducer configurations for use with different neck sizes. Ultrasound waves are generated using a piezoelectric source to the model of the airway and received by piezoelectric receivers on the opposite side. Energy, the area under the curve, and the peak value of the received signal, are used to detect the airway occlusion. RESULTS: The amount of reflected ultrasonic energy from the phantom model of the airway back to the transmitting transducer reduces as the airway model occlusion increases. Also, transmitted signal through the airway model increases as the amount occlusion of the airway model increases. CONCLUSIONS: The results of this study support the hypothesis that it is feasible to use ultrasonic pulses to detect partial and full upper airway occlusion.

A Multi-Camera System for Bioluminescence Tomography in Preclinical Oncology Research.

Bioluminescent imaging (BLI) of cells expressing luciferase is a valuable noninvasive technique for investigating molecular events and tumor dynamics in the living animal. Current usage is often limited to planar imaging, but tomographic imaging can enhance the usefulness of this technique in quantitative biomedical studies by allowing accurate determination of tumor size and attribution of the emitted light to a specific organ or tissue. Bioluminescence tomography based on a single camera with source rotation or mirrors to provide additional views has previously been reported. We report here in vivo studies using a novel approach with multiple rotating cameras that, when combined with image reconstruction software, provides the desired representation of point source metastases and other small lesions. Comparison with MRI validated the ability to detect lung tumor colonization in mouse lung.

Upper airway occlusion detection using a novel ultrasound technique.

Obstructive sleep apnea/hypopnea Syndrome (OSAHS) is the most common form of Sleep Disordered Breathing (SDB) and it is estimated to affect approximately 15% of US adult population. In this paper, we report on the results of in vivo experiments of an ultrasonic device for the non-invasive detection of obstructive sleep apnea/hypopnea (OSAH). A description of the ultrasonic system used is presented, followed by the results of a full night sleep study. The findings show a significant difference in the spectral features extracted from the received ultrasonic waveform during apneic breathing, compared to the hyperventilation that follows. Therefore, the findings indicate the feasibility of developing an ultrasonic detection device for low cost diagnosis of SDB.

In vivo characterization of ultrasonic transducers for the detection of airway occlusion in Sleep Disordered Breathing.

Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS) is the most common form of Sleep Disordered Breathing (SDB) and it is estimated to affect approximately 15% of US adult population. Various methods have been proposed for the development of inexpensive screening methods to detect SDB to reduce the need for costly nocturnal polysomnography (NPSG). In this paper, a description of the ultrasonic transducer design and characterization is presented, followed by the results of a full night sleep study. The findings show a significant difference in the temporal features extracted from the received ultrasonic waveform during apneic breathing, compared to the hyperventilation that follows. Therefore, the findings indicate the feasibility of developing an ultrasonic detection device for low cost diagnosis of SDB.

Detection of airway occlusion in simulated obstructive sleep apnea/hypopnea using ultrasound: an in vitro study.

Obstructive sleep apnea/hypopnea Syndrome (OSAHS) is the most common form of Sleep Disordered Breathing (SDB) and it is estimated to affect approximately 6% of US adult population. Various methods have been proposed for the development of inexpensive screening methods to detect SDB to reduce the need for costly nocturnal polysomnography (NPSG). By using the existing air in the airway as an ultrasonic contrast agent, we propose a method to examine the narrowing or occlusion of the airway associated with OSAHS events. We describe here an in vitro study that approximates the anatomical and acoustic characteristics of the airway and neck. In this experiment, we simulate the fully open airway as well as apnea and hypopnea events. These in vitro studies results show significant differences in the ultrasonic signals acquired from the open airway model versus those from the model depicting apnea and hypopnea events. Therefore, the findings provide a foundation for development of an ultrasound system to detect SDB in vivo.

Nanoparticulate radiolabelled quinolines detect amyloid plaques in mouse models of Alzheimer's disease.

Detecting aggregated amyloid peptides (Abeta plaques) presents targets for developing biomarkers of Alzheimer's disease (AD). Polymeric n-butyl-2-cyanoacrylate (PBCA) nanoparticles (NPs) were encapsulated with radiolabelled amyloid affinity (125)I-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) as in vivo probes. (125)I-CQ-PBCA NPs crossed the BBB (2.3 +/- 0.9 ID/g) (P < .05) in the WT mouse (N = 210), compared to (125)I-CQ (1.0 +/- 0.4 ID/g). (125)I-CQ-PBCA NP brain uptake increased in AD transgenic mice (APP/PS1) versus WT (N = 38; 2.54 x 10(5) +/- 5.31 x 10(4) DLU/mm(2); versus 1.98 x 10(5) +/- 2.22 x 10(4) DLU/mm(2)) and in APP/PS1/Tau. Brain increases were in mice intracranially injected with aggregated Abeta(42) peptide (N = 17; 7.19 x 10(5) +/- 1.25 x 10(5) DLU/mm(2)), versus WT (6.07 x 10(5) +/- 7.47 x 10(4) DLU/mm(2)). Storage phosphor imaging and histopathological staining of the plaques, Fe(2+) and Cu(2+), validated results. (125)I-CQ-PBCA NPs have specificity for Abeta in vitro and in vivo and are promising as in vivo SPECT ((123)I), or PET ((124)I) amyloid imaging agents.

Quinoline-n-butylcyanoacrylate-based nanoparticles for brain targeting for the diagnosis of Alzheimer's disease.

A survey of research activity on nanoparticles (NPs) based on polymeric devices that could cross the blood-brain barrier (BBB) is given along with the presentation of our own data on the development of NPs of n-butyl-2-cyanoacrylate (BCA) for brain delivery to aid the early diagnosis of Alzheimer's disease (AD), a neurodegenerative disorder of the elderly people, the most prevalent form of dementia. Typical data are presented on in vivo detection of amyloid peptides (A beta) (amyloid plaques) that are used as targets for developing the biological markers for the diagnosis of AD. In order to develop efficient in vivo probes, polymeric n-butyl-2-cyanoacrylate (PBCA) NPs have been prepared and encapsulated with the radio-labeled amyloid affinity drug (125)I-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) to improve the transport to brain and amyloid plaque retention of (125)I-CQ using the NPs of PBCA. The (125)I-CQ discriminately binds to the AD post-mortem brain tissue homogenates versus control. (125)I-CQ-PBCA NPs labeled the A beta plaques from the AD human post-mortem frontal cortical sections on paraffin-fixed slides. Storage phosphor imaging verified preferential uptake by AD brain sections compared to cortical control sections. The (125)I-CQ-PBCA NPs crossed the BBB in wild type mouse, giving an increased brain uptake measured in terms of % ID/g i.e., injected dose compared to (125)I-CQ. Brain retention of (125)I-CQ-PBCA NPs was significantly increased in the AD transgenic mice (APP/PS1) and in mice injected with aggregated A beta 42 peptide versus age-matched wild type controls. The results of this study are verified by in vivo storage phosphor imaging and validated by histopathological staining of plaques and select metal ions, viz. Fe(2+) and Cu(2+). The (125)I-CQ-PBCA NPs had more efficient brain entry and rapid clearance in normal mice and enhanced the retention in AD mouse brain demonstrating the ideal in vivo imaging characteristics. The (125)I-CQ-PBCA NPs exhibited specificity for A beta plaques both in vitro and in vivo. This combination offered radio-iodinated CQ-PBCA NPs as the promising delivery vehicle for in vivo single photon emission tomography (SPECT) ((123)I) or PET ((124)I) amyloid imaging agent. The importance of the topic in relation to brain delivery and other similar type of work published in this area are covered to highlight the importance of this research to medical disciplines.

Initiation of purinergic signaling by exocytosis of ATP-containing vesicles in liver epithelium.

Extracellular ATP represents an important autocrine/paracrine signaling molecule within the liver. The mechanisms responsible for ATP release are unknown, and alternative pathways have been proposed, including either conductive ATP movement through channels or exocytosis of ATP-enriched vesicles, although direct evidence from liver cells has been lacking. Utilizing dynamic imaging modalities (confocal and total internal reflection fluorescence microscopy and luminescence detection utilizing a high sensitivity CCD camera) at different scales, including confluent cell populations, single cells, and the intracellular submembrane space, we have demonstrated in a model liver cell line that (i) ATP release is not uniform but reflects point source release by a defined subset of cells; (ii) ATP within cells is localized to discrete zones of high intensity that are approximately 1 mum in diameter, suggesting a vesicular localization; (iii) these vesicles originate from a bafilomycin A(1)-sensitive pool, are depleted by hypotonic exposure, and are not rapidly replenished from recycling of endocytic vesicles; and (iv) exocytosis of vesicles in response to cell volume changes depends upon a complex series of signaling events that requires intact microtubules as well as phosphoinositide 3-kinase and protein kinase C. Collectively, these findings are most consistent with an essential role for exocytosis in regulated release of ATP and initiation of purinergic signaling in liver cells.

Practical method for radioactivity distribution analysis in small-animal PET cancer studies.

We present a practical method for radioactivity distribution analysis in small-animal tumors and organs using positron emission tomography imaging with a calibrated source of known activity and size in the field of view. We reconstruct the imaged mouse together with a source under the same conditions, using an iterative method, Maximum likelihood expectation-maximization with system modeling, capable of delivering high-resolution images. Corrections for the ratios of geometrical efficiencies, radioisotope decay in time and photon attenuation are included in the algorithm. We demonstrate reconstruction results for the amount of radioactivity within the scanned mouse in a sample study of osteolytic and osteoblastic bone metastasis from prostate cancer xenografts. Data acquisition was performed on the small-animal PET system, which was tested with different radioactive sources, phantoms and animals to achieve high sensitivity and spatial resolution. Our method uses high-resolution images to determine the volume of organ or tumor and the amount of their radioactivity has the possibility of saving time, effort and the necessity to sacrifice animals. This method has utility for prognosis and quantitative analysis in small-animal cancer studies, and will enhance the assessment of characteristics of tumor growth, identifying metastases, and potentially determining the effectiveness of cancer treatment. The possible application for this technique could be useful for the organ radioactivity dosimetry studies.

Advances in molecular imaging of pancreatic beta cells.

The development of non-invasive imaging methods for early diagnosis of beta cell associated metabolic diseases, including type 1 and type 2 diabetes (T1D and T2D), has recently drawn interest from the molecular imaging community and clinical investigators. Due to the challenges imposed by the location of the pancreas, the sparsely dispersed beta cell population within the pancreas, and the poor understanding of the pathogenesis of the diseases, clinical diagnosis of beta cell abnormalities is still limited. Current diagnostic methods are invasive, often inaccurate, and usually performed post-onset of the disease. Advances in imaging techniques for probing beta cell mass and function are needed to address this critical health care problem. A variety of imaging techniques have been tested for the assessment of pancreatic beta cell islets. Here we discuss current advances in magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and nuclear imaging for the study of beta cell diseases. Spurred by early successes in nuclear imaging techniques for beta cells, especially positron emission tomography (PET), the need for beta cell specific ligands has expanded. Progress for obtaining such ligands is presented. We report our preliminary efforts of developing such a peptidic ligand for PET imaging of pancreatic beta cells.

Vascular imaging of solid tumors in rats with a radioactive arsenic-labeled antibody that binds exposed phosphatidylserine.

PURPOSE: We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of vascular endothelial cells in tumors, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we tested the hypothesis that a chimeric monoclonal antibody that binds phosphatidylserine could be labeled with radioactive arsenic isotopes and used for molecular imaging of solid tumors in rats. EXPERIMENTAL DESIGN: Bavituximab was labeled with (74)As (beta(+), T(1/2) 17.8 days) or (77)As (beta(-), T(1/2) 1.6 days) using a novel procedure. The radionuclides of arsenic were selected because their long half-lives are consistent with the long biological half lives of antibodies in vivo and because their chemistry permits stable attachment to antibodies. The radiolabeled antibodies were tested for the ability to image subcutaneous Dunning prostate R3227-AT1 tumors in rats. RESULTS: Clear images of the tumors were obtained using planar gamma-scintigraphy and positron emission tomography. Biodistribution studies confirmed the specific localization of bavituximab to the tumors. The tumor-to-liver ratio 72 h after injection was 22 for bavituximab compared with 1.5 for an isotype-matched control chimeric antibody of irrelevant specificity. Immunohistochemical studies showed that the bavituximab was labeling the tumor vascular endothelium. CONCLUSIONS: These results show that radioarsenic-labeled bavituximab has potential as a new tool for imaging the vasculature of solid tumors.

Antivascular effects of combretastatin A4 phosphate in breast cancer xenograft assessed using dynamic bioluminescence imaging and confirmed by MRI.

Bioluminescence imaging (BLI) has found significant use in evaluating long-term cancer therapy in small animals. We have now tested the feasibility of using BLI to assess acute effects of the vascular disrupting agent combretastatin A4 phosphate (CA4P) on luciferase-expressing MDA-MB-231 human breast tumor cells growing as xenografts in mice. Following administration of luciferin substrate, there is a rapid increase in light emission reaching a maximum after about 6 min, which gradually decreases over the following 20 min. The kinetics of light emission are highly reproducible; however, following i.p. administration of CA4P (120 mg/kg), the detected light emission was decreased between 50 and 90%, and time to maximum was significantly delayed. Twenty-four hours later, there was some recovery of light emission following further administration of luciferin substrate. Comparison with dynamic contrast-enhanced MRI based on the paramagnetic contrast agent Omniscan showed comparable changes in the tumors consistent with the previous literature. Histology also confirmed shutdown of tumor vascular perfusion. We believe this finding provides an important novel application for BLI that could have widespread application in screening novel therapeutics expected to cause acute vascular changes in tumors.

The use of histone deacetylase inhibitor FK228 and DNA hypomethylation agent 5-azacytidine in human bladder cancer therapy.

The long-term disease-free survival in patients with metastatic transitional cell carcinoma (TCC) is still considerably low. Novel chemotherapeutic agents are needed to decrease the morbidity and mortality of TCC. In this study, we have evaluated several epigenetic modifiers for their therapeutic application in bladder cancer. Both histone deacetylase inhibitors (FK228, TSA) and DNA hypomethylating agent (5-Azacytidine) were tested using in vitro assays such as cell viability, cell cycle analysis and western blot to determine their mechanisms of action. Drug combination experiments were also designed to study any additive or synergistic effects of these agents. In addition, two bladder cancer xenograft models (one subcutaneous and one orthotopic) were employed to assess the therapeutic efficacy of these agents in vivo. Three agents exhibited various growth inhibitory effects on 5 different TCC cell lines in a dose- and time-dependent manner. In addition to G2/M cell cycle arrest, FK228 is more potent in inducting apoptosis than the two other single agents, and combination of both FK228 and 5-Aza further enhances this effect. p21 induction is closely associated with FK228 or TSA but not 5-Aza, which is mediated via p53-independent pathway. Consistent with in vitro results, FK228 exhibited a significant in vivo growth inhibition of TCC tumor in both subcutaneous and orthotopic xenograft models. FK228 is a potent chemotherapeutic agent for TCC in vivo with minimal undesirable side effects. The elevated p21 level mediated via p53 independent pathway is a hallmark of FK228 mechanism of action.

Iterative reconstruction method for light emitting sources based on the diffusion equation.

Bioluminescent imaging (BLI) of luciferase-expressing cells in live small animals is a powerful technique for investigating tumor growth, metastasis, and specific biological molecular events. Three-dimensional imaging would greatly enhance applications in biomedicine since light emitting cell populations could be unambiguously associated with specific organs or tissues. Any imaging approach must account for the main optical properties of biological tissue because light emission from a distribution of sources at depth is strongly attenuated due to optical absorption and scattering in tissue. Our image reconstruction method for interior sources is based on the deblurring expectation maximization method and takes into account both of these effects. To determine the boundary of the object we use the standard iterative algorithm-maximum likelihood reconstruction method with an external source of diffuse light. Depth-dependent corrections were included in the reconstruction procedure to obtain a quantitative measure of light intensity by using the diffusion equation for light transport in semi-infinite turbid media with extrapolated boundary conditions.

Dermatan carriers for neovascular transport targeting, deep tumor penetration and improved therapy.

A new approach to functional tumor imaging and deep interstitial penetration of therapeutic agents is to target the upregulated transport activities of neovascular endothelium. Agents are formulated with the anionic glycosaminoglycan, 435-type dermatan sulfate (DS 435, 22.2 kDa), chemically enriched for oligosaccharide sequences that confer high heparin cofactor II binding and correlate with high tumor uptake. A magnetic resonance (MR) imaging agent is prepared as self-assembling, 5-nm nanoparticles of Fe(+3):deferoxamine (Fe:Df) bound by strong ion pairing to DS, which forms the outer molecular surface (Zeta potential -39 mV). On intravenous (i.v.) injection, Fe:Df-DS rapidly (<7 min) and selectively targets and transports at high capacity across the neovascular endothelium of large (2-cm) Dunning prostate R3327 AT1 rat tumors; releases from the abluminal surface, due to reversible binding of its multivalent, low-affinity (K(d) 10(-4) to 10(-5)) oligosaccharide ligands; and progressively penetrates the interstitium from its initial site of high uptake in the well-perfused outer tumor rim, into the poorly perfused central subregion. By gamma camera imaging of (67)Ga:Df-DS, the agent avoids normal site uptake and clears through the kidneys with a t(1/2) of 18 min. A therapeutic formulation of DS-doxorubicin (DS-dox) is prepared by aqueous high-pressure homogenization of the drug and DS 435, which produces 11-nm nanoparticles of doxorubicin cores coated with DS (Zeta potential -39 mV) that are stable to lyophilization. Microscopic analysis of tumor sections 3 h after i.v. injection shows much higher overall tumor fluorescence and deeper matrix penetration for DS-dox than conventional doxorubicin (dox): >75 vs. <25 microm between the nearest microvessels. DS-dox also results in enhanced tumor-cell internalization and nuclear localization of the drug. Therapeutic efficacies in established (250 +/- 15 mg) MX-1 human breast tumor xenografts at maximum tolerated doses (MTDs) are (control vehicle, dox, dox-DS) (a) median days to 7-fold tumor growth: 8.3, 25.6 (p = 0.0007), 43.2 (p = 0.0001); (b) complete 90-day tumor regressions: 0/10, 0/10, 4/10. These results demonstrate the potential to develop a novel class of carbohydrate-targeted neovascular transport agents for sensitive, high-resolution (100-microm) MR imaging and improved treatment of larger sized human tumor metastases.

Targeted nanoparticles for drug delivery through the blood-brain barrier for Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia among the elderly, affecting 5% of Americans over age 65, and 20% over age 80. An excess of senile plaques (beta-amyloid protein) and neurofibrillary tangles (tau protein), ventricular enlargement, and cortical atrophy characterizes it. Unfortunately, targeted drug delivery to the central nervous system (CNS), for the therapeutic advancement of neurodegenerative disorders such as Alzheimer's, is complicated by restrictive mechanisms imposed at the blood-brain barrier (BBB). Opsonization by plasma proteins in the systemic circulation is an additional impediment to cerebral drug delivery. This review gives an account of the BBB and discusses the literature on biodegradable polymeric nanoparticles (NPs) with appropriate surface modifications that can deliver drugs of interest beyond the BBB for diagnostic and therapeutic applications in neurological disorders, such as AD. The physicochemical properties of the NPs at different surfactant concentrations, stabilizers, and amyloid-affinity agents could influence the transport mechanism.

Reduction in normalized bone elasticity following long-term bisphosphonate treatment as measured by ultrasound critical angle reflectometry.

Using an improved version of ultrasound critical angle reflectometry, the bone quality of cortical and trabecular bone was assessed in vivo by measuring elastic moduli (normalized for bone density) at both principal axes, referred to as the minimum and maximum normalized elasticities. The measurements were made in 30 normal premenopausal women, 30 normal postmenopausal women, 22 untreated postmenopausal women with osteoporosis, 74 postmenopausal women with osteoporosis or osteopenia on bisphosphonate treatment, and 32 patients with renal transplantation (16 women and 16 men) taking steroids. Cortical elasticity was higher than trabecular elasticity; both declined slightly and non-significantly with age in normal women. Among untreated postmenopausal women with osteoporosis, cortical maximum normalized elasticity (E(cmax)) remained within 95% prediction intervals of normal women. Among patients on bisphosphonate, E(cmax) was low in the majority of patients. E(cmax) was significantly more depressed among those taking the drug > or =3 years than <3 years (22.1% below normal premenopausal women versus 17.2%, P =0.001), and among those with incident non-spinal fractures than without (75.9 vs. 81.5%, P =0.008). E(cmax) was independent of bone mineral density at the calcaneus. Most patients with renal transplantation had low E(cmax), with a mean 20.8% below the normal premenopausal mean. Qualitatively similar findings were found with cortical minimum elasticity and with trabecular minimum and maximum elasticities. Thus, the material bone quality of cortical and trabecular bone may be impaired following bisphosphonate treatment, as in renal transplantation on steroids.

Validating bioluminescence imaging as a high-throughput, quantitative modality for assessing tumor burden.

Bioluminescence imaging (BLI) is a highly sensitive tool for visualizing tumors, neoplastic development, metastatic spread, and response to therapy. Although BLI has engendered much excitement due to its apparent simplicity and ease of implementation, few rigorous studies have been presented to validate the measurements. Here, we characterize the nature of bioluminescence output from mice bearing subcutaneous luciferase-expressing tumors over a 4-week period. Following intraperitoneal or direct intratumoral administration of luciferin substrate, there was a highly dynamic kinetic profile of light emission. Although bioluminescence was subject to variability, strong correlations (r >.8, p <.001) between caliper measured tumor volumes and peak light signal, area under light signal curve and light emission at specific time points were determined. Moreover, the profile of tumor growth, as monitored with bioluminescence, closely resembled that for caliper measurements. The study shows that despite the dynamic and variable nature of bioluminescence, where appropriate experimental precautions are taken, single time point BLI may be useful for noninvasive, high-throughput, quantitative assessment of tumor burden.

Molecular imaging in prostate cancer.

Prostate cancer (PCa) is the most common non-cutaneous malignancy in men. New ways to diagnose this cancer in its early stages are needed. Unique genetic and biochemical changes in the cell pave the way for tumors to grow and metastasize. Novel imaging approaches attempt to detect pathological processes in cancer cells at the molecular level. This has led to the establishment and development of the field of molecular imaging. Positron emission tomography (PET), magnetic resonance spectroscopic imaging (MRSI), magnetic resonance imaging (MRI), and radiolabeled antibodies are a few of the modalities that can detect abnormal tumor metabolic processes in the clinical setting. Other imaging techniques are still in their early phase of development but hold promise for the future, including bioluminescence imaging (BLI), measurement of tumor oxygenation, and measurement of uptake of iodine by tumors. These techniques are non-invasive and can spare the patient undue morbidity, while potentially providing early diagnosis, accurate follow-up and, finally, valuable prognostic information.

Tumor oximetry: comparison of 19F MR EPI and electrodes.

We recently described a novel approach to measuring regional tumor oxygen tension. This approach is based on 19F pulse burst saturation recovery NMR echo planar imaging relaxometry of hexafluorobenzene or "FREDOM" (Fluorocarbon Relaxometry using Echo planar imaging for Dynamic Oxygen Mapping). We have now compared oxygen tension measurements using FREDOM with a traditional polarographic method (the Eppendorf Histograph) in a group of size matched Dunning prostate rat tumors R3327-AT1. We also compare MR and electrode approaches to monitoring dynamic changes with respect to interventions and demonstrate extension of the MR technique to rat breast tumors.