Keywords: Alzheimer's Disease, Alzheimer's Disease, Intermittent theta-burst stimulation (iTBS)

Motivation: Addressing the global AD crisis by investigating CT-iTBS as a non-pharmacological treatment to enhance memory and cognition.

Goal(s): To explore the therapeutic efficacy and determine the optimal treatment protocol of CT-iTBS in AD while unveiling its potential underlying mechanism for enhancing memory and cognitive functions.

Approach: Utilized brain magnetic resonance imaging analysis, behavioral tests, and immunofluorescence staining for assessing the therapeutic effect of different durations of CT-iTBS treatment.

Results: Prolonged CT-iTBS significantly enhanced cognitive and memory behaviors, altered brain functional connectivity, promoted a neuroprotective effect, and reduced amyloid accumulation in AD mouse model. These findings present a promising therapeutic avenue for AD patients.

Impact: Our findings revealed a highly promising avenue for enhancing the quality of life for individuals with AD and provided insights into the potential underlying neuroprotective mechanisms of CT-iTBS in alleviating memory deficits.

Keywords: Small Animals, Focused Ultrasound, MR-guided FUS, Multiparametric MRI

Motivation: Long-term delivery of therapeutic agents via repeated MRgFUS is an innovative approach for enhancing glioblastoma treatment but underlying mechanisms are not well documented.

Goal(s): Find the best strategy for long-term drug delivery after multiple MRgFUS mediated BBB opening.

Approach: Repeated MRgFUS treatments were delivered up to 8 sessions over one month along with a multi-parametric MRI protocol follow-up to measure physiological, hemodynamic and oxygenation parameters in order to assess the safety and effectiveness of the procedure.

Results: Intensive, repeated treatments, may lead to tissue modifications that require attention and limit the frequency of ultrasound mediated drug delivery to once a week.

Impact: Long-term delivery of therapeutics through a FUS-induced permeabilized BBB redefines therapeutic strategies as it improves patient outcomes. To ensure the best translation towards clinical treatment, evaluation of hemodynamics and oxygenation modifications in the CNS is necessary to refine treatment parameters.

Keywords: Biology, Models, Methods, Cancer, Biomarker

Motivation: Cancer immunotherapy with cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) agonists aims to generate an immune response by T cell priming, activation and infiltration into the tumour microenvironment leading to cell death.

Goal(s): The clinical development of STING agonists would benefit from imaging biomarkers that inform on intratumoural pharmacodynamics and potentially anti-tumour response.

Approach: Longitudinal diffusion-weighted MRI in a thyroid xenograft model indicated sustained increase in ADC as an imaging biomarker of tumour microenvironment changes following treatment with a STING agonist.

Results: The potential use of MRI as an indicator of early STING pathway related pharmacodynamic effects in situ is demonstrated.

Impact: Increased ADC is a sensitive, clinically-translatable imaging biomarker of tumour response to a STING agonist.

Keywords: Small Animals, Hyperpolarized MR (Gas), RILI, radiation, CSSR

Motivation: Chemical shift saturation recovery (CSSR) measurements are incredibly useful for quantifying pulmonary gas exchange and uptake; because CSSR is a spectroscopic technique, however, such measures are only global in nature. 

Goal(s): Our goal was to develop an imaging-based technique for spatially-resolving CSSR measurements.

Approach: We demonstrated our technique’s utility in a rodent model of radiation-induced lung injury.

Results: Images of hyperpolarized-129Xe dissolved in the pulmonary membrane (Mem) and red blood cells (RBC) showed higher Mem signal and reduced RBC signal in radiated vs non-radiated lungs. Septal wall thickness (SWT) measurements derived on a quadrant level also revealed elevated SWT in the irradiated region.

Impact: We demonstrated a new imaging technique for regionally quantifying radiation-induced alterations in pulmonary gas exchange and uptake. This study lays the groundwork for future investigations aimed at improving radiotherapy strategies, mitigating radiotoxicity, and treating radiation-associated illness. 

Keywords: Probes & Targets, Multimodal, theranostic, temperature probe, fluorine

Motivation: Theranostic materials allows for simultaneous therapeutic and diagnostic disease intervention.

Goal(s): We aimed to engineer a protein-based theranostic with multiple imaging modalities.

Approach: Using noncannonical amino acid incorporation of trifluoroleucine (TFL), we synthesize fluorinated coiled-coil, Q2_TFL, imageable by ¹H MRI and high-frequency ultrasound, and sensitive to ¹⁹F MRS.

Results: Q2_TFL demonstrates reduced signal contrast in ¹H MRI, echogenic signals under high-frequency ultrasound, and enhances sensitivity in linear ratiometric ¹⁹F MRS. This allows for thermoresponsiveness and potential protein conformation analysis. Q2_TFL serves as a promising platform for versatile and effective theranostic agents, bringing together therapeutic and diagnostic modalities in a compact and efficient manner.

Impact: Q2TFL, a fluorinated protein fiber, enables drug delivery and offers unique multimodal imaging. It acts as a temperature probe and protein structure monitor, paving the way for innovative theranostic biomaterials.

Keywords: Probes & Targets, MR-Guided Interventions, Glioblastoma, Mesenchymal stem cells

Motivation: Immunotherapy resistance in glioblastoma (GBM) has been linked to a paucity of tumor-infiltrating T lymphocytes and concurrent T-cell dysfunction.

Goal(s): This research aims to determine whether MRI-visible mesenchymal stem cells (MSCs) could be employed for GBM immunotherapy.

Approach: CXCL10-Nrf2-FTH-MSCs with enhanced T lymphocyte recruitment (Cxcl10 gene), oxidative stress tolerance (Nrf2 gene), and MRI visibility (Fth gene) were genetically engineered. With the guidance of FTH-MRI, these MSCs were injected into the tumor periphery of orthotopic GL261 GBMs in mice.

Results: In vivo MRI monitoring and histology examinations demonstrated that CXCL10-Nrf2-FTH-MSCs can significantly limit GBM growth by reviving T lymphocytes within the tumor.

Impact: FTH-MRI is a practical method for guiding intracranial stem cell transplantation. MRI-guided peritumoral implantation of CXCL10-Nrf2-FTH-MSCs provides a novel immunotherapeutic approach based on tumoricidal stem cells for the treatment of GBM.

Keywords: Biology, Models, Methods, Cancer, BTK inhibition, mantle cell lymphoma models, early metabolic biomarker of response, 1H MRS with slice selective double frequency Hadamard Selective Multiple Quantum Coherence transfer pulse sequence, STEAM pulse sequence

Motivation: The current approaches to assess Bruton’s kinase inhibitor (BTK) therapeutic effects in cancer are not ideal. 

Goal(s): Employing metabolic imaging, we evaluated the mode of action of ibrutinib (IBR), a BTK inhibitor, in mantle cell lymphoma (MCL) cells and xenografts.

Approach: Our approach using ¹H MRS demonstrated that, in sensitive MCL models, IBR significantly impacted critical metabolic pathways, including glycolysis, glutaminolysis, and phospholipid metabolism, but had far less of an impact on IBR-poorly responsive cells.

Results: Changes in ¹H MRS detectable lactate, alanine, and choline concentrations on various MCL models emerged as promising biomarkers of response or resistance to IBR.

Impact: Decreased intra-tumoral concentrations of lactate, alanine, and choline measured by ¹H MRS during treatment can potentially become early and sensitive biomarkers of BTK inhibition in MCL and, likely, other lymphoma treatments.

Keywords: Small Animals, Cancer, cancer immunotherapy, gas-photothermal therapy, magnetic resonance imaging, stimulator of interferon genes pathways, triple-negative breast cancer

Motivation: Breast cancer exhibits high incidence and mortality rates. We reports a functional nanosystem composed of Pluronic F127, manganese chloride (MnCl₂), and IR780 dye. The nanosystem possesses multimodal imaging capabilities using near-infrared II (NIR-II) and T1-T2 dual-enhanced MRI, guiding photothermal therapy, and enhancing the STING pathway to combat triple-negative breast cancer.

Goal(s): Effectively suppress TNBC growth and metastasis, with good biocompatibility..

Approach: MC@NS nanosystem could diagnose the tumor and confirm the time window of treatment via NIR II/MRI dual-modal imaging, and effectively suppress tumor growth thought phototherapy, STING pathway and anti-tumor immunity.

Results: It effectively suppress tumor growth thought phototherapy, STING pathway and immunotherapy. 

Impact: This nanosystem, through T1-T2 dual-enhanced MRI and NIR II multimodal imaging, enabled tumor diagnosis and guided photothermal therapy, effectively suppressing tumor growth by combining photothermal therapy and STING pathway to enhance immunogenic cell death, providing a novel theranostic strategy.

Keywords: Probes & Targets, Cancer

Motivation: Molecular imaging holds revolutionary significance in the diagnosis and treatment of tumors. 

Goal(s): Clinical trials targeting immune checkpoint receptors with immune checkpoint blockade (ICB) therapies has encountered limited efficacy in pancreatic cancer.

Approach: MRI-guide ICB therapy (MRGIT) strategy for enhancing and guiding anti-PD-L1 therapy was proposed.

Results: The successful inhibition of tumor growth via MRGIT strategy in pancreatic tumor models demonstrates that it may be efficiently reverse the immunosuppressive PDAC and improve the ICB therapy with the employment of MRI technology.

Impact: The MRGIT strategy bridging the antitumor immune response with the MRI technique, which devised a potent tool that holds great promise for improving cancer diagnosis and facilitating the development of personalized treatment strategies tailored to individual patients.

Keywords: Preclinical Image Analysis, Nervous system

Motivation: Predicting Tumor-Associated Macrophages (TAMs)  levels using preoperative non-invasive imaging can influence patients with Glioblastoma (Gb) treatment decision-making and evaluate prognosis.

Goal(s): This study aimed to combine imaging and radiomics features of preoperative for predicting CD68 + macrophage infiltration.

Approach: Retrospective collection 143 patients with Gb. Divided patients into high CD68+TAMs（≥14.8%）and low CD68+TAMs (<14.8%) groups. The radiomics features extraction were based on CE-T1WI and T2WI. Multi-parameter stepwise regression was used to create the models.

Results: The combined model, with ADCmin and radiomics features, had the best performance revealing AUCs of 0.865 and 0.825 for the training and testing sets, respectively. 

Impact: To provide imaging biomarkers for the evaluation of the TAMs infiltration of Gb by using machine learning combined with MR imaging parameters, reveal the relationship between images features and TAMs, and construct an evaluation model to predict macrophage before surgery.