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<title>Electron Paramagnetic Resonance (EPR) Imaging of in-vivo Oxygen Status Associated with Cancer Treatment Studies | National Institute of Biomedical Imaging and Bioengineering</title>
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<article data-history-node-id="136316" about="/labs-at-nibib/ideas-lab/projects/electron-paramagnetic-resonance-epr-imaging-vivo-oxygen-status-associated-cancer-treatment-studies" class="ideas-projects node--ideas-projects node--type-ideas-projects">
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||
</div>
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<div class="field--items grid-row flex-row">
|
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<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
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<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>R Andrew Byrd, Ph.D.</span></div>
|
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||
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||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Structural Biophysics Laboratory, Center for Cancer Research, NCI</div>
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||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
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||
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||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Janusz Koscielniak, Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Structural Biophysics Laboratory, Center for Cancer Research, NCI</div>
|
||
|
||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
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||
|
||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>James Mitchell, Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Radiation Biology Branch, Center for Cancer Research, NCI</div>
|
||
|
||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
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|
||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Nallathamby Devasahayam</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Radiation Biology Branch, Center for Cancer Research, NCI</div>
|
||
|
||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
||
|
||
|
||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Murali Krishna Cherukuri, Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Radiation Biology Branch, Center for Cancer Research, NCI</div>
|
||
|
||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
||
|
||
|
||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Benes Trus, Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">High Performance Computing and Informatics Office, Office of Intramural Research, CIT</div>
|
||
|
||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
||
|
||
|
||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Anthony Fletcher, Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">High Performance Computing and Informatics Office, Office of Intramural Research, CIT</div>
|
||
|
||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
||
|
||
|
||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Calvin Johnson, Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">High Performance Computing and Informatics Office, Office of Intramural Research, CIT</div>
|
||
|
||
</div>
|
||
</span>
|
||
</div>
|
||
<div class="affiliations margin-top-205">
|
||
<button type="button" class="usa-button btn btn-primary toggle">See Affiliations</button>
|
||
<ol>
|
||
</ol>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
<div class="ideas-project-section-title">
|
||
<h2>Project Brief</h2>
|
||
</div>
|
||
|
||
|
||
<div class="field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>In this collaboration, EPR imaging technology is demonstrated to be a novel physiological imaging modality useful in obtaining maps of tissue oxygenation quantitatively and non-invasively with high spatial and temporal resolution. In vivo EPR imaging has been successfully implemented in small animal experiments, specifically in mouse models of human cancer to obtain information (e.g., dynamics of tumor physiology, hypoxia) critical for treatment selection (e.g., chemotherapy, anti-angiogenic drug therapy, and radiotherapy) and response monitoring. The capabilities of EPR imaging have been found to be very useful in screening anti-cancer agents, as well as understanding their mechanisms. The NIH development team, NCI Radiation Biology Branch and CIT SPIS, has designed and implemented several EPR imaging systems capable of in vivo imaging, which is often combined via co-registration with anatomic images from MRI.</p>
|
||
<p>The imaging systems and methodologies (e.g., microscopic histopathology for microvessel analysis) are utilized by many NIH scientists. Prior techniques, which provided such information, are either invasive or not quantitative, and there is no equivalent commercially available EPR imaging system. In contrast to MRI, EPR imaging requires lower radio-frequency (RF) power levels, faster data acquisition rates, and very sensitive detectors. SPIS engineering and prototyping expertise has been critical to addressing these hardware and software design requirements.</p>
|
||
<p>More recently, the team is evaluating integration of error-correcting codes (i.e. Hadamard, Frank, and Chu sequences), often used in telecommunication systems operating within noisy environments, with the EPR pulse sequences in an effort to reduce transmit power levels. Instead of a single high-power RF transmit pulse, hundreds of lower power pulses are generated, and a single acquisition sample is obtained between pulses. These low power pulses are modulated using an error-correcting code, and the samples are correlated with the same code to extract the free induction decay signal (FID).</p>
|
||
<p>The team is also working on an EPR method called Rapidscan. Until recently, EPR systems were either continuous wave (CW) or pulsed. Rapidscan EPR is a newer modality that is distinct from the more established methods.</p>
|
||
<ul>
|
||
<li>CW EPR – constant RF signal, constant gradient fields, varying B0 field</li>
|
||
<li>Pulsed EPR – pulsed RF signal, constant gradient fields, constant B0 field</li>
|
||
<li>Rapidscan EPR – constant RF signal, varying gradient fields, varying B0 field</li>
|
||
</ul>
|
||
<p>Rapidscan EPR has some of the best attributes of the other two modalities. It offers the sensitivity of CW EPR and the faster data acquisition rates of pulsed EPR. Since the RF signal is constant, data acquisition is not hampered by dead time and coil resonant ringing. The gradient and B0 fields oscillate sinusoidally making them simple to generate. Overall, the hardware requirements for Rapidscan EPR are easier to achieve.</p>
|
||
<p> </p>
|
||
|
||
<figure role="group" class="align-center">
|
||
<img alt="A photo of computers, devices, and electrical equipment in a lab" data-entity-type="file" data-entity-uuid="93f593e1-a42a-448d-9b8d-ea1d999f8d2f" height="602" src="/sites/default/files/inline-images/Fig1.png" width="803" loading="lazy">
|
||
<figcaption>One of several custom pulsed EPR imaging systems. The two racks on the right contain commercially available amplifiers to drive the main field and gradient field coils. The rack on the left contains a combination of custom electronics, designed and built in-house, and commercially available equipment to generate and receive the RF signals. The EPR instrument main, gradient, and sample coils are located behind the three racks.</figcaption>
|
||
</figure>
|
||
<p> </p>
|
||
<div style="margin:2em auto;width:80%;">
|
||
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d="M256.21,531.49v-.79c-.39,.62-.97,.93-1.74,.93-.5,0-.95-.14-1.37-.41s-.74-.66-.97-1.15-.34-1.05-.34-1.69,.1-1.18,.31-1.69,.52-.89,.93-1.16,.88-.4,1.39-.4c.38,0,.71,.08,1,.24s.53,.36,.71,.62v-3.08h1.05v8.59h-.98Zm-3.33-3.11c0,.8,.17,1.39,.5,1.79s.73,.59,1.19,.59,.85-.19,1.17-.57,.48-.95,.48-1.73c0-.85-.16-1.48-.49-1.88s-.73-.6-1.21-.6-.86,.19-1.17,.57-.47,.99-.47,1.81Z" /><path d="M260,531.49l-1.9-6.22h1.09l.99,3.59,.37,1.34c.02-.07,.12-.49,.32-1.28l.99-3.64h1.08l.93,3.61,.31,1.19,.36-1.2,1.07-3.6h1.03l-1.95,6.22h-1.1l-.99-3.73-.24-1.06-1.26,4.79h-1.1Z" /><path d="M267.52,524.11v-1.21h1.05v1.21h-1.05Zm0,7.38v-6.22h1.05v6.22h-1.05Z" /><path d="M274.22,531.49v-.79c-.39,.62-.97,.93-1.74,.93-.5,0-.95-.14-1.37-.41s-.74-.66-.97-1.15-.34-1.05-.34-1.69,.1-1.18,.31-1.69,.52-.89,.93-1.16,.88-.4,1.39-.4c.38,0,.71,.08,1,.24s.53,.36,.71,.62v-3.08h1.05v8.59h-.98Zm-3.33-3.11c0,.8,.17,1.39,.5,1.79s.73,.59,1.19,.59,.85-.19,1.17-.57,.48-.95,.48-1.73c0-.85-.16-1.48-.49-1.88s-.73-.6-1.21-.6-.86,.19-1.17,.57-.47,.99-.47,1.81Z" /><path d="M279.16,530.55l.15,.93c-.3,.06-.56,.09-.8,.09-.38,0-.68-.06-.89-.18s-.36-.28-.45-.48-.13-.61-.13-1.25v-3.58h-.77v-.82h.77v-1.54l1.05-.63v2.17h1.06v.82h-1.06v3.64c0,.3,.02,.49,.06,.58s.1,.15,.18,.21,.2,.08,.36,.08c.12,0,.27-.01,.46-.04Z" /><path d="M280.19,531.49v-8.59h1.05v3.08c.49-.57,1.11-.86,1.86-.86,.46,0,.86,.09,1.2,.27s.58,.43,.73,.75,.22,.79,.22,1.39v3.94h-1.05v-3.94c0-.53-.11-.91-.34-1.15s-.55-.36-.97-.36c-.31,0-.61,.08-.88,.24s-.47,.38-.59,.66-.18,.66-.18,1.15v3.4h-1.05Z" /></g></g></svg><p style="background-color:#ececec;padding:1em;">Block diagram of the RF subsystems within the custom pulsed EPR imaging system. The transmit box and receive box are custom-built in-house using commercially available RF components. The RF transmitter section outputs the signals through the diplexer to the EPR sample coil. The receive signals from the coil (i.e., free induction decay signals) pass through the diplexer to the RF receiver section for pre-processing before input into the data acquisition hardware.</p>
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</div>
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<p> </p>
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<figure role="group" class="align-center">
|
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<img alt="Pulsed EPR imaging of three phantom tubes, blue and teal dots with red in the middle of some of them" data-entity-type="file" data-entity-uuid="708ec977-a6a0-497a-b90f-f64381ecc247" height="149" src="/sites/default/files/inline-images/Fig3.png" width="852" loading="lazy">
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<figcaption>EPR imaging of three phantom tubes utilizing (a) the single high power RF pulse method, (b) low power RF pulses modulated with a 256-element Hadamard sequence, (c) low power RF pulses modulated with a 256-element Frank sequence, and (d) low power RF pulses modulated with a 256-element Chu sequence. Correction of hardware limitations will improve the Frank and Chu sequence image reconstructions.</figcaption>
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</figure>
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<p> </p>
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<figure role="group" class="align-center">
|
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<img alt="Pulsed EPR imaging methods: Single high-power RF pulse vs. Train of low-power RF pulses" data-entity-type="file" data-entity-uuid="acd7221d-722d-4489-b52a-9fb7c36d5a58" height="332" src="/sites/default/files/inline-images/Fig4a.jpg" width="610" loading="lazy">
|
||
<figcaption>(a) Traditional EPR transmit and receive sequence. A strong RF pulse is generated, and the FID signal is received and sampled. A Fourier Transform is then applied to generate the projections used to form an image. (b) Novel EPR acquisition. A series of low power RF pulses are generated each of which is modulated based on an error-correcting code. A single sample is acquired after each pulse. The samples are then correlated with the error-correcting code. A Fourier Transform is then applied to generate the projections used to form an image.</figcaption>
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</figure>
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<p> </p>
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<div>
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<div class="field field--name-field-card-text field--type-text-long field--label-hidden field__item"><ul>
|
||
<li><a href="https://pubmed.ncbi.nlm.nih.gov/30579225/">Towards reduction of SAR in scaling up in vivo pulsed EPR imaging to larger objects</a></li>
|
||
<li><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2084379/">A new strategy for fast radiofrequency CW EPR imaging: Direct detection with rapid scan and rotating gradients</a></li>
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<li><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847784/">Integration of digital signal processing technologies with pulsed electron paramagnetic resonance imaging</a></li>
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<li><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1805680/">Direct detection and time-locked subsampling applied to pulsed electron paramagnetic resonance imaging</a></li>
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<li><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3512196/">Stochastic excitation and Hadamard correlation spectroscopy with bandwidth extension in RF FT-EPR</a></li>
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||
<li><a href="https://pubmed.ncbi.nlm.nih.gov/10089172/">High-Speed Data Acquisition System and Receiver Configurations for Time-Domain Radiofrequency Electron Paramagnetic Resonance Spectroscopy and Imaging</a></li>
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<li><a href="https://pubmed.ncbi.nlm.nih.gov/10089172/">High Speed Digitizer/Averager Data Acquisition System for Fourier Transform Electron Paramagnetic Resonance Spectroscopy</a></li>
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<li><a href="https://www.sciencedirect.com/science/article/abs/pii/S106418668371071X">Radiofreqency FT-EPR Spectroscopy and Imaging</a></li>
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<div class="field field--name-field-card-text field--type-text-long field--label-hidden field__item"><p>Patent: <a href="https://patents.google.com/patent/US5502386">Pulsed low frequency EPR spectrometer and imager</a></p>
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<div class="field field--name-field-card-text field--type-text-long field--label-hidden field__item"><p>2016 CIT Director’s Merit Award</p>
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<h2>Capabilities</h2>
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<a href="/labs-at-nibib/ideas-lab/capabilities">See All IDEAS Capabilities</a>
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