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| 4528.
| 49 | Tumor-induced metabolic reprogramming and CD8+ T-cell exhaustion of the spleen James D Barnett1, Marie-France Penet 1,2, Raj Kumar Sharma1, Michal Stanczak3, Saleem Yousf1, Balaji Krishnamachary1, Yelena Mironchik1, Erika L Pearce3, and Zaver M Bhujwalla1,2,4 1Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD, United States, 2Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States, 3Bloomberg-Kimmel Institute of Immunotherapy, Baltimore, MD, United States, 4Department of Radiation Oncology and Molecular Radiation Sciences, Baltimore, MD, United States Keywords: Probes & Targets, Tumor, Spleen Motivation: Metastasis is the leading cause of cancer-related mortality worldwide. We must pave new avenues for cancer treatment by interrogating the pro-tumorigenic properties of the tumor macroenvironment. Goal(s): We seek to investigate how tumorigenesis metabolically impacts the spleen microenvironment and how it contributes to immune evasion. Approach: Proton magnetic resonance spectroscopy was used to identify aqueous spleen metabolites during tumorigenesis. Flow cytometric analyses were conducted to immunophenotype splenic CD8+ T cells and to quantify MDSC and T-cell frequencies. Results: Tumorigenesis induced common, distinct metabolite changes in mouse spleens. Flow cytometric analyses revealed splenic CD8-T-cell exhaustion and reduced cytotoxic T-cell effector function. Impact: Tumors drive metabolic spleen alterations that may contribute to reduced CD8+ T cells and their exhaustion even
before reaching the tumor, contributing to immune suppression and poor
prognosis. This may provide metabolism-targeted strategies to
improve immune surveillance and immunotherapy. |
| 4529.
| 50 | Evaluation of Biochemically Recurrent Prostate Cancer Using the Prostate Imaging for Recurrence Reporting Systems xiang liu1, Jun Shen2, and Kan Deng3 1department of radiology, Sun Yat-Sen Memorial Hospital, Guangzhou, China, 2Sun Yat-Sen Memorial Hospital, Guangzhou, China, 3Philips Healthcare, Guangzhou, China Keywords: Preclinical Image Analysis, Preclinical, Prostate Imaging for Recurrence Reporting; Prostate cancer; Recurrence; Interreader agreement. Motivation: PI-RR assessment is not universally validated and has not yet been extensively studied for diagnostic accuracy and interreader variability. Goal(s): To evaluate the performance of PI-RR for detecting local recurrence in PCa patients with BCR after radiation therapy (RT) or radical prostatectomy (RP). Approach: 110 patients who underwent MRI and FDG PET/CT were included. A group of four radiologists with varying experience was recruited for recurrence evaluation. Results: With a PI-RR of 3 as a cutoff, the AUCs ranged from 0.56 to 0.83 after RT and 0.73 to 0.90 after RP across the four readers. The ICC values were 0.54 and 0.68, respectively. Impact: PI-RR may serve as a clinical guide to improve the management of recurrent PCa by achieving good diagnostic performance and interreader agreement. |
| 4530.
| 51 | Detection Efficiency of 18F-PSMA-1007 PET/CT and Multi-parameter MRI in Prostate Cancer and Its Correlation with Pathological Grade Zhou Yunshu1, Chen Zhiqiang2, Zhang ruodi1, Liu Shili1, Chen Xiaohua1, Wang Aijun3, and Xiong Yuhui4 1Clinical medicine school of Ningxia Medical University, Yinchuan, China, 2Department of Radiology, The First Hospital Affiliated to Hainan Medical College, Haikou, China, 3Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, China, 4GE Healthcare MR Research, Beijing, China Keywords: Preclinical Image Analysis, Tumor, prostate cancer Motivation: The combination of MRI imaging and PSMA PET/CT imaging has attracted more and more attention. Goal(s): Therefore, this study will compare the diagnostic value of 18F-PSMA-1007 PET/CT imaging and multi-parameter MRI alone and in combination with prostate cancer. Approach: This study retrospectively collected the clinical, imaging and pathological data of 50 patients with prostate disease who underwent mp-MRI and 18F-PSMA-1007PET/CT examination in our hospital. Results: We found that the combination of 18F-PSMA-1007 PET/CT and multi-parameter MRI can improve the diagnostic efficiency of prostate cancer. ADC value, SUVmax and SUVmax/ADC can distinguish between low-risk and medium-high-risk prostate cancer. Impact: The diagnostic efficacy of combined multi-parameter MRI (ADC) and 18F-PSMAPET/CT (SUVmax) is better than that of ADC, SUVmax and SUVmax/ADC with higher sensitivity and specificity. The combination of these two imaging modalities can complement each other and improve the accuracy. |
| 4531.
| 52 | Whole body imaging at 3T with multi-coil array and compressed sensing for metastasis screening with cryo-fluorescence tomography validation. Orlando Aristizabal1, Nicole Eskow2, Neelam Pandya1, Eva Hernando Monge2, and Youssef Zaim Wadghiri1 1Radiology, New York University School of Medicine, New York, NY, United States, 2Pathology, New York University School of Medicine, New York, NY, United States Keywords: Biology, Models, Methods, Whole Body, compressed sensing; metastasis; fluorescence tomography Motivation: Cancer metastasis involves multiple organs and traditional bioluminescent imaging lacks spatial resolution to locate metastatic foci. New MRI imaging protocols need to be developed to image metastasis distribution over the whole mouse body. Goal(s): - Acquire high resolution 3D volumes in an acceptable time frame.
- Validate findings using cryo-fluorescence tomography (CFT).
Approach: - An 8-channel array coil was used to acquire whole body isotropic volumes with compressed sensing.
- Post imaging CFT datasets were acquired for validation.
Results: - High contrast volumes of mouse body were acquired at 200x200x200 μm in 16 minutes.
- Liver metastatic foci observed.
- Correspondence of mouse anatomy with MRI and CFT achieved.
Impact: Whole body imaging with 8-channel array coil permits longitudinal visualization of major organs in normal and diseased states. Compressed sensing optimizes workflow for high throughput screening, and Cryo-Fluorescence tomography can then be used as gold standard for validation of MRI. |
| 4532.
| 53 | Enhancement of Radiation Therapy Response in Prostate Cancer by Metabolic Modulation Stepan Orlovskiy1, Pradeep Kumar Gupta1, David Nelson1, Fernando Arias-Mendoza1,2, Vivek Narayan1, Ming You3, Balaraman Kalyanaraman3, Cameron Koch1, and Kavindra Nath1 1University of Pennsylvania, Philadelphia, PA, United States, 2Advanced Imaging Research, Inc., Cleveland, OH, United States, 3Medical College of Wisconsin, Milwaukee, WI, United States Keywords: Other Preclinical, Molecular Imaging, Prostate Cancer Models, Lonidamine, mito-Lonidamine, 1H and 31P MRS, Seahorse, oxygen consumption rate, pH Motivation: When prostate cancer is treated with external beam radiation therapy (RT) with doses up to 78 Gy, gastrointestinal and genitourinary toxicities are often observed. Goal(s): Tumor sensitization by mito-lonidamine (mito-LND) will lower RT doses reducing the risk of adverse effects. Approach: The effects were assessed in vitro and in vivo in prostate cancer models using Seahorse, 1H and 31P MRS respectively. Results: Our findings showed a sustained and tumor-selective decrease in intracellular pH, bioenergetics, oxygen consumption rate and lactate. Selective tumor acidification, deenergization and oxygenation induced by mito-LND may improve the radiation response in prostate cancer. Impact: Exploiting the modulation of
tumor metabolism and microenvironment for improving therapeutic efficacy of radiation
therapy (RT) in early stage prostate cancer will lead to improved outcomes in
prostate cancer patients. |
| 4533.
| 54 | Repeatability of a quantitative multiparametric MRI protocol for imaging hypoxia, cellularity, and perfusion in a murine model of glioblastoma Ayesha Das1, David Hormuth1,2, Jack Virostko2,3,4,5, and Thomas Yankeelov1,2,3,4,5,6 1Biomedical Engineering, University of Texas at Austin, Austin, TX, United States, 2Oden Institute for Computational Science and Engineering, University of Texas at Austin, Austin, TX, United States, 3Diagnostic Imaging, Dell Medical School, Austin, TX, United States, 4Livestrong Cancer Institutes, Dell Medical School, Austin, TX, United States, 5Oncology, Dell Medical School, Austin, TX, United States, 6Imaging Physics, MD Anderson Cancer Center, Houston, TX, United States Keywords: Preclinical Image Analysis, Quantitative Imaging, hypoxia Motivation: Heterogeneous distributions of hypoxic tissues lead to divergent radiotherapy response. Thus, developing a practical, accurate, and reproducible method of quantifying hypoxia is of great interest. Goal(s): Establish a repeatable, multiparametric MRI protocol for quantifying hypoxia. Approach: We induced C6 brain tumors in rats and conducted test-retest TOLD-MRI, DCE-MRI, and DW-MRI exams on each rat. We then analyzed the MRI data to identify spatially distinct physiological clusters within the tumor. Results: An initial assessment of repeatability of hypoxia, normoxia, and necrotic tissue localization within a tumor. Impact: Developing a quantitative and repeatable protocol for quantifying tumor hypoxia will have immediate applications in studies seeking to design, assess, and optimize radiotherapy regimens. |
| 4534.
| 55 | Assessing host-tumour vasculature and glycolytic metabolism in response to hypoxia in a chick CAM model of GBM using MRI and MRS Elisabeth Non Tudor Gash1,2, Sarah E Barnett3, Mahon Maguire2, Stephen Pickup4, Sonia Rocha5, Judy M Coulson1, and Harish Poptani1,2 1Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, United Kingdom, 2Centre for Preclinical Imaging, Liverpool Shared Research Facilities, University of Liverpool, Liverpool, United Kingdom, 3Egg Facility, Liverpool Shared Research Facilities, University of Liverpool, Liverpool, United Kingdom, 4Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, 5Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, United Kingdom Keywords: Biology, Models, Methods, Cancer, Glioblastoma, hypoxia, vasculature, metabolism, chick embryo CAM model Motivation: Understanding vasculature, hypoxia and glycolysis in GBM is paramount towards understanding its resistance to therapies, but cannot be done in vitro. The CAM model is attractive as it provides the interaction between host vasculature and the tumour. Goal(s): Optimise MRI and MRS to assess hypoxia, tumour-host vasculature and glycolytic metabolism in the GBM-CAM. Approach: GBM-CAM xenografts were created under normoxic- and hypoxic-conditions. Imaging was performed using microscopy and MRI, and lactate detection via MRS. Results: Distinct morphological differences in vasculature were identified between conditions. MRI revealed vessel penetration, MRS detected lactate levels, which were significantly higher in hypoxic tumours than in the CAM. Impact: Developing tools to characterise vascular morphology and quantify lactate levels in the CAM GBM model can shed light on fundamental biological mechanisms, and support the development of therapeutic strategies for the clinic. |
| 4535.
| 56 | Inverse Z-spectrum analysis of chemical exchange saturation transfer MRI in orthotopic models of paediatric-type diffuse high grade glioma. Declan J. Bolster1, Upasana Roy1, Rita Pereira2, Ketty Kessler2, Chris Jones2, Simon P. Robinson1, and Jessica K. R. Boult1 1Division of Radiotherapy & Imaging, Institute of Cancer Research, London, United Kingdom, 2Division of Molecular Pathology, Institute of Cancer Research, London, United Kingdom Keywords: Biology, Models, Methods, Cancer, Preclinical; CEST & MT Motivation: The diffuse growth of paediatric-type diffuse high grade glioma (PDHGG) precludes complete delineation with conventional MRI. Goal(s): Molecular imaging with CEST may improve tumour detection. Approach: Three orthotopic models of PDHGG were assessed using inverse Z-spectrum analysis of CEST data. Results: Clear distinction between tumour and contralateral normal-appearing brain in ssMT and rNOE maps, which relate to macromolecular content, was observed in two well-defined tumour models when analysed using MTRRex and AREX. Similar CEST contrast was also apparent in a third more diffuse model, inconspicuous on T2w-MRI. This CEST approach can successfully stratify PDHGG tumours in vivo. Impact: Relaxation compensated CEST metrics provide novel biochemical contrasts in three orthotopic models of paediatric-type diffuse high grade glioma, enabling detection of diffuse disease, highlighting the clinical potential of CEST contrasts to stratifying tumours. |
| 4536.
| 57 | MRI Assessment of Sensitivity to Carbon Ion Irradiation in Rat C6 Glioma Yu Feng Li1 and Jian Li Liu1,2 1Department of Radiology, Lanzhou University Second Hospital, Lanzhou, Gansu, China, 2Lanzhou University Second Hospital, Lanzhou, Gansu, China Keywords: Tumors (Post-Treatment), Animals Motivation: What is the specific efficacy of carbon ion radiation in the treatment of brain gliomas? Goal(s): To assess the specific effect of carbon ion irradiation in inhibiting the growth and peritumor infiltration of gliomas. Approach: Establishment of a rat C6 brain glioma model with carbon ion irradiation and assessment of the efficacy response of brain glioma after carbon ion irradiation using MRI multiparametric imaging Results: MRI multiparametric imaging can reflect the inhibitory effect of carbon ion irradiation on the growth and invasion of gliomas. Impact: CIRT for glioma is still in the stage of
clinical trials, the number of subjects is limited, and its specific efficacy
still needs to be explored. Our study provides an experimental basis for the clinical application of CIRT for gliomas. |
| 4537.
| 58 | EPR imaging of oxygen consumption driven by NQO1-activated compounds in FH-deficient renal tumors Yuki Shibata1, Daniel R Crooks1, Shun Kishimoto1, Jeeva Munasinghe2, Kristofer Ervin2, Jeffrey Brender3, Murali C Krishna3, and William Marston Linehan1 1Urologic Oncology Branch, National Cancer Institute, National Institution of Health, Bethesda, MD, United States, 2National Institute of Neurological Disorders and Stroke, National Institution of Health, Bethesda, MD, United States, 3Radiation Biology Branch, National Cancer Institute, National Institution of Health, Bethesda, MD, United States Keywords: Preclinical Image Analysis, Electron Paramagnetic Resonance Motivation: Renal tumors in patients affected by Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) are aggressive and metastasize early. The high expression of NAD(P)H quinone oxidoreductase 1 (NQO1) in HLRCC could be a therapeutic target. Goal(s): Our goal was to determine if NQO1-activated substrates can be used as a therapeutic approach for HLRCC renal tumors. Approach: In vitro experiments and EPR, DCE, and photoacoustic imaging were performed to study the effect of NQO1-activated substrates on oxygen levels and tumor growth in HLRCC. Results: Our study demonstrated by EPR imaging that oxygen consumption is induced by NQO1-activated substrates, resulting in ROS production and tumor cytotoxicity. Impact: We found that NQO1-activated substrates induced non-mitochondrial oxygen consumption in FH-deficient renal tumor cells, triggering oxidative stress-induced cancer cell death. Our results suggest a promising path for NQO1-targeted therapy in HLRCC, necessitating further research and treatment development. |
| 4538.
| 59 | EPR imaging assessment of reduced tumor oxygenation induced by HIF-2a inhibitor Belzutifan in VHL-deficient renal cell carcinoma models Kazumasa Horie1, Shun Kishimoto1, Kota Yamashita1, Kazutoshi Yamamoto1, Jeffery R Brender1, Nallanthamby Devasahayam1, Hellmut Merkle2, Murali C Krishna1, and W Marston Linehan1 1NCI, Bethesda, MD, United States, 2NINDS, Bethesda, MD, United States Keywords: Preclinical Image Analysis, Electron Paramagnetic Resonance Motivation: In the previous study, EPR oximetry unveiled physiological responses to a VEGF inhibitor, but the potential of EPR oximetry in upstream inhibition of the HIF pathway remained unclear. Goal(s): To determine if Belzutifan, a HIF-2α inhibitor, affects tumor oxygenation as measured by EPR oximetry and to offer a non-invasive biomarker of its therapeutic efficacy. Approach: Three xenograft models of clear cell carcinoma were treated with Belzutifan and changes in tumor oxygen levels were assessed using EPR oximetry. Results: We observed significant alterations in tumor oxygenation exclusively in responding tumors, which we attributed to diminished VEGF expression. Impact: This research underlines the significance of EPR oximetry as a non-invasive tool to detect early responses to HIF-2α inhibitors like Belzutifan, which could profoundly affect the management and therapeutic approach for cancer treatment, guiding personalized medicine. |
| 4539.
| 60 | Evaluating vascular normalization in orthotopic triple negative breast cancer with metronomic chemotherapy using 3D-UTE-GRASP DCE MRI Sawwal Qayyum1, Jin Zhang1, Eric Aronowitz2, Myung Shin Han1, Seung Koo Lee1, and Gene Kim1 1Radiology, Weill Cornell Medical, New York City, NY, United States, 2Citigroup Biomedical Imaging Center, Weill Cornell Medical, New York City, NY, United States Keywords: Preclinical Image Analysis, Modelling, Breast, Cancer, Vascular, Image Reconstruction Motivation: Metronomic chemotherapy shows promise as a cost-effective therapy for vascular normalization. However, it is unclear how to determine the optimal biological dose (OBD). Goal(s): Our goal is to use dynamic contrast-enhanced (DCE) MRI and pharmacokinetic analysis for non-invasive measurements of the heterogenous tumor treatment response toward determining the OBD. Approach: The 4T1 murine orthotopic triple negative breast cancer models were assessed longitudinally using two different dosing schemes, daily and intermittent, using cyclophosphamide. Pharmacokinetic and histological analysis (CD31, Ki67) were conducted. Results: The intermittent dosing schedule showed higher Vp, Fp, and Ktrans in all tumor regions indicating possible vascular normalization. Impact: The proposed 3D-UTE-GRASP DCE-MRI method provides a non-invasive
platform to assess for optimal biological dose in metronomic chemotherapy. By
accurately determining the heterogenous tumor vessel dynamical changes, this
platform can be used to enhance treatment response over time. |
| 4540.
| 61 | Comparison of breast cancer subtypes in treatment response using Dynamic Contrast-Enhanced MRI Sawwal Qayyum1, Jin Zhang1, Eric Aronowitz2, Myung Shin Han1, Seung Koo Lee1, and Gene Kim1 1Radiology, Weill Cornell Medical, New York City, NY, United States, 2Citigroup Biomedical Imaging Center, Weill Cornell Medical, New York City, NY, United States Keywords: Biology, Models, Methods, Breast, Vascular, Image Reconstruction, Cancer Motivation: Breast cancer molecular subtype may affect therapeutic efficacy of metronomic chemotherapy, which currently has not been investigated with non-invasive methods. Goal(s): This study is to utilize DCE-MRI for quantitative measurement of treatment response in different breast cancer subtypes. Approach: Preclinical orthotopic models 67NR(ER+) and 4T1(triple negative) of breast cancer were treated with the same metronomic chemotherapy, while the heterogenous treatment response was evaluated using DCE-MRI. Results: In both tumor models, treatment induced higher Vp, Fp, and Ktrans. The 67NR tumors had higher vascular measures with slower growth rates than the 4T1 tumors. Impact: The preliminary data in this study suggest that the tumor volume
alone does not provide adequate information about the changes induced by
treatment, and the treatment response differs substantially between breast
cancer subtypes as observed by DCE-MRI parameters. |
| 4541.
| 62 | Quantitative MRI Measurements Record Pancreatic Cancer and Stroma Reactions to New KRAS Inhibitor Mamta Gupta1, Hoon Choi1, Samantha B Kemp2, Emma E Furth2, Miguel Joaquim1, Stephen Pickup1, Cynthia Clendenin2, Margo Orlen2, Thomas B Karasic2, Hee Kwon Song1, Yong Fan1, Peter O’ Dwyer2, Robert H. Vonderheide2, Mark A Rosen1, Ben Z. Stanger2, and Rong Zhou1 1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States Keywords: Small Animals, Cancer, Treatment Response Motivation: KRAS mutations occur in 90% of pancreatic ductal adenocarcinoma(PDA) with G12Dmutation being the most common.Recent KRAS(G12D) inhibitors have unraveled an exciting therapeutic opportunity for this deadly cancer,as they are being tested in clinical trials. Goal(s): However, the prior use of KRAS(G12C)inhibitors in lung cancer treatment showed mere 50% patient response,despite the accurate genetic mutation,calling for biomarkers which can assess the drug-target engagement early on and predict treatment outcome. Approach: To test the utility of translational MRI markers in a clinically relevant PDA model for early responses to KRAS(G12D) inhibitor,MRTX1133. Results: ADC,Ktrans and MTR captured MRTX1133 induced early cancer cell death and stroma change. Impact: Our
study in genetically engineered mouse model of pancreatic cancer supports that clinical
translatable MRI metrics (ADC, Ktrans and MTR) are promising for capturing
early pharmacodynamic responses to KRAS inhibitor MRTX1133. |
| 4542.
| 63 | Prediction model based on MRI morphological features for distinguishing benign and malignant thyroid nodules Tingting Zheng1 and Bin Song1 1Fudan University Minhang Hospital, Shanghai, China Keywords: Biology, Models, Methods, Head & Neck/ENT Motivation: The low specificity of many Thyroid Imaging Reporting and Data Systems (TI-RADSs) lead to a large number of unnecessary biopsies. Goal(s): This study developed and validated a predictive model based on MRI morphological features to improve the specificity. Approach: A retrospective analysis was conducted on 825 thyroid nodules pathologically confirmed postoperatively. Univariate and multivariate logistic regression was used to obtain β coefficients, construct predictive models and nomogram incorporating MRI morphological features in the training cohort, and validated in a validation cohort. Results: Compared with the TI-RADSs, predictive models have better specificity along with a high sensitivity and can reduce unnecessary biopsies. Impact: predictive models have better specificity along with a high sensitivity and may avoid numerous invasive needle biopsies |
| 4543.
| 64 | Targeting Extradomain-B Fibronectin to Monitor Immune Checkpoint Therapy with MRI in Head and Neck Squamous Cell Carcinoma Ryan Hall1, Hong Wang2, Victoria Laney1, and Zheng-Rong Lu1 1Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, 2Biomedical Engineering, Case Western Reserver University, Cleveland, OH, United States Keywords: Probes & Targets, Cancer Motivation: Only 15-20% of patients with advanced head and neck squamous cell carcinoma (HNSCC) benefit from immunotherapy, with no reliable strategies to quickly predict or determine a patient’s response to treatment. Goal(s): We aim to evaluate a therapeutic monitoring strategy using MRI by targeting extradomain B fibronectin (EDB-FN) in the tumor stroma. Approach: Using mouse models bearing HNSCC allografts, we treated and monitored therapeutic efficacy of anti-PDL1 immunotherapy with MRI using MT218, our EDB-FN-targeted contrast agent. Results: Treatment-responsive tumors exhibited unique expression patterns of EDB-FN compared to controls that were visualized with MT218 MRI, demonstrating the potential for predicting and monitoring HNSCC immunotherapy response. Impact: We demonstrate that EDB-FN is a potential biomarker for immunotherapy response in HNSCC, and our MRI strategy targeting EDB-FN offers clinicians a potential method for predicting or monitoring immunotherapeutic outcomes to improve the clinical management of HNSCC. |