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(FL^1­­)].

Approach: Develop a PET/MRI probe, [¹⁸F][Gd(FL^1­­)], 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(FL^1­­)] 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.

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.

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.

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.

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.

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 (v_e/v_b) in the case of subtle BBB impairment.

Approach: The v_e/v_b 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 v_e/v_b 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.

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.

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.