ISSN# 1545-4428 | Published date: 19 April, 2024
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At-A-Glance Session Detail
   
Novel Contrast Agents & Innovative Modellings
Oral
Contrast Mechanisms
Wednesday, 08 May 2024
Room 331-332
15:45 -  17:45
Moderators: Celia Martinez de la Torre & Andreas Loening
Session Number: O-28
CME Credit

15:45 Introduction
Celia Martinez de la Torre
Memorial Sloan Kettering Cancer Center, New York, NY, United States
15:571038.
A Novel PET/MRI Hybrid Probe enables Non-invasive Imaging of Perfusion and Excretion in vivo
Remy Chiaffarelli1,2, Jan Kretschmer1,2, Jonathan Cotton1,2, Miloslav Polasek3, and André Martins1,2,4
1Werner Siemens Imaging Center, University Hospital Tuebingen, Tuebingen, Germany, 2Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Tuebingen, Germany, 3Institute of Organic Chemistry and Biochemistry of the CAS, Prague, Czech Republic, 4German Cancer Consortium (DKTK), partner site Tübingen, German Cancer Research Center (DKFZ), Heidelberg, Germany

Keywords: Contrast Agents, PET/MR, Perfusion Kidney Gadolinium

Motivation: Our work is driven by the conviction that the integration of PET and MRI in molecular imaging has the potential to revolutionize diagnostic precision and patient care.

Goal(s): Enhance precision molecular imaging through the development of a unique hybrid PET/MRI perfusion probe, [18F][Gd(FL1­­)].

Approach: Develop a PET/MRI probe, [18F][Gd(FL1­­)], that is exceptionally stable, rapidly synthesized, efficiently radiolabeled, and allows simultaneous PET/MR imaging, focusing on tissue perfusion and renal filtration in preclinical models.

Results: After achieving high-yield radiosynthesis with a unique approach, our dual-modality probe showed consistent signals in both imaging modalities and was reliably quantified thanks to the combination of PET and MRI.

Impact: The first-of-its-kind hybrid PET/MR probe [18F][Gd(FL1­­)] can be readily and efficiently radio-synthetized and allows simultaneous PET/MR quantitative measurement of perfusion and excretion. This probe opens the path for quantifying molecular imaging probes in research and clinical practice.

16:091039.
Non-invasive magnetic resonance imaging agent for in-vivo detection of cardiac fibrosis.
Kyle David William Vollett1,2, Anlan Hong1,2, and Hai-Ling Margaret Cheng1,2,3
1Biomedical Engineering, University of Toronto, Toronto, ON, Canada, 2Ted Rogers Centre for Heart Research, University of Toronto, Toronto, ON, Canada, 3Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada

Keywords: Contrast Agents, Molecular Imaging, fibrosis, myocardium, hypertension, diabetes

Motivation: Fibrosis is a progressive pathological process that contributes to 45% of deaths worldwide and is associated with the accumulation of collagen and the destruction of tissue architecture. While progression of fibrosis is often slow, early detection is difficult, leading to intervention at late stage when transplant may be the only option.

Goal(s): Establish a targeted MRI contrast agent for detecting early fibrosis.

Approach: Validation of agent sensitivity in-vivo with isoproterenol-induced heart fibrosis in a mouse model.

Results: Our novel fibrosis agent surpassed the sensitivity and specificity of Gd contrast enhanced T1 mapping for detecting mild cardiac fibrosis.

Impact: This project sets out to create a new, hitherto inaccessible window on fibrogenesis, providing a new paradigm for diagnosing patients with fibrosis and the study of anti-fibrosis intervention before fibrosis becomes extensive and irreversible.

16:211040.
Nanodiamonds as a novel T1-contrast agent for MRI
Jelena Lazovic1 and Metin Sitti1
1Intelligent Systems, Max Planck Institute, Stuttgart, Germany

Keywords: Novel Contrast Mechanisms, Contrast Agent, nanodiamonds, cell labeling

Motivation: The structural defects in diamond particles, are known for their paramagnetic properties. Here we aim to determine if the presence of paramagnetic centers in detonation nanodiamonds particles can be exploited to enhance longitudinal relaxation time (T1).

Goal(s): Introduce nanodiamonds as a novel T1-contrast agent and contrast differences with gadolinium chelates.

Approach: Using high-field, 7 T MRI, longitudinal and transverse relaxation rates were measured and compared between detonation and air-oxidized detonation nanodiamonds. In-vivo demonstration was carried out using chicken embryos. 

Results: Air-oxidized detonation nanodiamonds have superior longitudinal and transverse relaxivity compared to detonation nanodiamonds. We demonstrate their potential as an alternative, gadolinium-free T1-contrast agent.

Impact: Nanodiamonds hold great promise for biomedical applications mostly due to their biocompatibility, non-toxicity and versatile functionalization. A possibility for direct visualization by means of T1-weighted MRI is opening new venues for tracking over time without a concern for Gd3+-toxicity.

16:331041.
Molecular MRI of neuroinflammation using a redox-active iron complex
Chunxiang Zhang1,2, Can Zhang3, Eric M. Gale1, and Iris Y. Zhou1
1Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA, United States, 2Department of Radiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China, 3Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Diseases (MIND), Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA, United States

Keywords: Contrast Agents, Contrast Agent, Neuroinflammation

Motivation: Neuroinflammation is a critical pathophysiological process implicated in the development of neurodegenerative disorders.  

Goal(s): Imaging to detect, monitor, and surveil neuroinflammatory processes could profoundly improve how patients suffering neurodegenerative diseases are diagnosed and managed.

Approach: We evaluated brain imaging with the oxidatively activated contrast agent, Fe-PyC3A, as a proxy for inflammatory microglial activity in a mouse model of lipopolysaccharide(LPS)-induced neuroinflammation.

Results: Fe-PyC3A generated significantly greater enhancement in LPS-treated mice than in saline-treated controls, correlating with immunohistochemical quantification of microglial activation. Imaging using Gd-DOTA as negative control probe and NOX-2 deficient mice as loss of function control links Fe-PyC3A enhancement with reactive microglial activity.

Impact: MRI using oxidatively activated probes as a potential marker to detect and quantify neuroinflammatory processes could profoundly improve how patients suffering neurodegenerative diseases are diagnosed and managed.

16:451042.
T1 relaxometry or EPR signal intensity – Which is best for quantifying iron oxide nanoparticles in tissues non-destructively?
Saurin Kantesaria1, Xueyan Tang1, Steven Suddarth1, Jacqueline Pasek-Allen1, Bat-Erdene Namsrai1, Arjun Goswitz1, Mikaela Hintz1, John Bischof1, and Michael Garwood1
1University of Minnesota, Minneapolis, MN, United States

Keywords: Electron Paramagnetic Resonance, Electron Paramagnetic Resonance, iron oxide nanoparticles, T1 relaxometry

Motivation: Currently there is no low-cost method to nondestructively quantify iron oxide nanoparticles (IONPs) in tissue across a wide concentration range (0.05-100 mg Fe/mL).

Goal(s): Our lab has developed a low-cost, LOngitudinally Detected Electron Paramagnetic Resonance (LOD-EPR) system. This work aims to evaluate LOD-EPR IONP quantification accuracy.

Approach: We compare IONP Fe quantification accuracy of R1 (=1/T1) from MR relaxometry versus LOD-EPR signal in solution and IONP-perfused rat kidney sections used in cryopreservation.

Results: LOD-EPR signal vs Fe concentration is linear in 0.05-10 mg Fe/mL IONP solutions and in IONP-perfused tissue, whereas R1 vs Fe concentration is linear in solution but not in tissue.

Impact: Accurate quantification of IONPs in tissues at room temperature can be done using low-cost, benchtop LOD-EPR. Our primary application is in IONP rewarming of cryopreserved organs, however other applications such as dosimetry and oxygen sensing should also be possible.

16:571043.
Validating DCE-MRI estimates of leakage volumes associated with subtle blood-brain barrier dysfunction using two-photon microscopy.
Martin Kozár1,2, Sarah Al-Bachari3, Laura Parkes2,4, Hervé Boutin5,6, Ingo Schiessl2,6, and Ben R Dickie1,2
1Division of Informatics, Imaging, and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom, 2Geoffrey Jefferson Brain Research Center, Manchester Academic Health Science Center, The University of Manchester, Manchester, United Kingdom, 3University College London, London, United Kingdom, 4Division of Psychology, Communication and Human Neuroscience, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom, 5UMR 1253, iBrain, Inserm, Bat Planiol, UFR de Médecine, Université de Tours, Tours, France, 6Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom

Keywords: Contrast Agents, DSC & DCE Perfusion

Motivation: DCE-MRI can be used to quantify subtle blood-brain barrier disruption. In this setting, it is generally assumed that contrast agent has access to the entire interstitial space. Prior work from our group indicates that contrast agent has access to a leakage volume much smaller than the interstitial space.

Goal(s): To provide independent validation of DCE-MRI leakage-to-vessel volume ratios (ve/vb) in the case of subtle BBB impairment.

Approach: The ve/vb ratio of Sulphorhodamine-101 (MW = 606.7g/mol) was measured in mouse brain using two-photon microscopy and compared to DCE-MRI estimates.

Results: The ve/vb ratio of sulphorhodamine-101 agrees well with DCE-MRI estimates.

Impact: Our results indicate that DCE-MRI kinetic models that assume infinite leakage volume (e.g. Patlak model) do not accurately reflect how Gd-DOTA distributes within the brain when BBB impairment is subtle.

17:091044.
A novel mathematical model to quantify tumor fluid properties on longitudinal breast DCE-MRI for neoadjuvant chemotherapy response assessment
Xinan Chen1, Wei Huang2, Amita Shukla-Dave1,3, Ramesh Paudyal1, Allen Tannenbaum4, and Joseph Deasy1
1Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 2Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, 3Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 4Applied Mathematics & Statistics and Computer Science, Stony Brook University, Stony Brook, NY, United States

Keywords: Contrast Agents, Perfusion, Modelling, Tumors, Biomarkers, Quantitative Imaging

Motivation: To advance the field of pharmacokinetic analysis of breast DCE-MRI by developing a model accounting for inter-fluid transport within tumor tissue

Goal(s): To develop a novel DCE-MRI pharmacokinetic method to quantify and visualize fluid flows in tumors and identify predictive imaging biomarkers of therapeutic response to neoadjuvant chemotherapy (NACT) in breast cancer. 

Approach: We developed a mathematical model in computational fluid dynamics termed the unbalanced regularized optimal mass transport (urOMT)

Results: Our urOMT model provides fluid transport properties of the tumor using breast DCE-MRI; the urOMT-derived quantitative metrics may be future predictive imaging biomarkers to measure treatment effectiveness in patients treated with NACT.

Impact: We developed a novel mathematical model to quantify, track, and visualize fluid flows in tumors with breast DCE-MRI data. The proposed quantitative metrics after validation may serve as predictive imaging biomarkers for breast cancer patients treated with neoadjuvant chemotherapy.

17:211045.
A correction for modeling of radial, spiral, and PROPELLOR DCE data: time-averaged extended Tofts
Natalia V Korobova1, Marian A Troelstra1, and Oliver J Gurney-Champion1
1Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, Netherlands

Keywords: Contrast Agents, DSC & DCE Perfusion, Perfusion, Pharmacokinetics, Body, Liver, DCE, Diagnosis

Motivation: Accurate quantification of pharmacokinetic parameters in dynamic contrast-enhanced (DCE) MRI requires high temporal resolution, often reached through non-cartesian sampling patterns that oversample the center of k-space (e.g. radial, spiral, PROPELLOR). In pharmacokinetic models, image contrast is assumed to be formed instantly at discrete time-points. However, in acquisitions oversampling the k-space center, the signal per time-frame becomes an average over acquisition time.

Goal(s): To correct for the time-averaged signals.

Approach: We proposed a modification to DCE modeling and tested it in simulations and in-vivo.

Results: Modern sampling patterns predominantly affect the pharmacokinetic parameter estimates for longer sampling times (>8s) per DCE frame.

Impact: We verified that for short acquisitions per frame (<8s) per DCE-frame, conventional Toft's modeling is sufficient. However, for longer sampling times (>8s) per DCE frame, our time-averaged extended Toft's model is needed for accurate estimations of pharmacokinetic parameters.

17:33 Discussion
Celia Martinez de la Torre
Memorial Sloan Kettering Cancer Center, New York, NY, United States