Keywords: Tumors (Pre-Treatment), Tumor, IDH1 mutation, glioma, MEGA-PRESS, 2-Hydroxyglutarate, glutamate, GABA, glutathione

Motivation: Detecting isocitrate dehydrogenase 1 (IDH1) mutations via in vivo MRI can significantly aids glioma diagnosis and treatment strategies.

Goal(s): To investigates the use of MEGA-PRESS sequences to non-invasively charaterize the metabolic profile of IDH1 mutation glioma. 

Approach: We measured 2-hydroxyglutarate (2HG), glutamate+glutamine (GLX), GABA and glutathione (GSH) inside the glioma from an IDH1(R132H)-mutant and an IDH1-wildtype murine models.

Results: The results unveil distinctive metabolic changes in IDH1 mutation tumors, including elevated 2HG, GLX/GABA ratio, and reduced GSH. These findings offer potential biomarkers for precise diagnosis and therapeutic strategies, highlighting the significant role of MEGA-PRESS in the studies of glioma.

Impact: The study identifies 1H MRS-based biomarkers for non-invasive detection of IDH1 mutation tumors using the MEGA-PRESS sequence. It provides insights into metabolic changes and neurochemical imbalances, aiding early diagnosis, treatment guidance, and monitoring, thus advancing precision oncology.

Keywords: Small Animals, Cancer, MRS, IVIM, treatment response

Motivation: There is a lack of comprehensive understanding regarding the impact of choline kinase inhibition and standard chemotherapy on preclinical GBM models.

Goal(s): The primary goal of this study was to elucidate the treatment response mechanism in a preclinical GBM mouse model.

Approach: MRS and IVIM-DWI were used for monitoring metabolic and microstructural changes in a preclinical GBM model by single or combination therapy with a choline kinase inhibitor and TMZ.

Results: Our findings indicate that the combination therapy is the most effective treatment regimen. This study contributes to a better understanding of treatment response mechanisms and underscores the potential of non-invasive MRI methods.

Impact: Targeting ChoKα inhibition and the damage of DNA replication (TMZ) promises to be an alternative in the treatment of GBM. This research also highlights the importance of MRS and IVIM-DWI as promising non-invasive methods to assess therapeutic effects on GBM.

Keywords: Biomarkers, Cancer, Prostate, Metabolism

Motivation: MRI agents that can monitor abnormal glutamine utilization, a hallmark of many aggressive cancers, are not clinically available. 

Goal(s): We investigated the utility of glutamine as a chemical exchange saturation transfer (CEST) agent to evaluate its utilization. 

Approach: Phantoms revealed contrast differences between glutamine and its metabolic products. Dynamic CEST images (in vivo) were acquired in 2 prostate cancer xenograft models after intravenous injection of glutamine. MALDI (matrix-assisted laser desorption/ionization) images of the same tumors (ex vivo) were collected for validation.

Results: CEST and MALDI images could distinguish prostate tumors derived from cell lines with known differences in glutamine utilization.

Impact: The potential of CEST (chemical exchange saturation transfer) MRI to evaluate glutamine utilization was evaluated in preclinical prostate cancer models (DU-145 and LNCaP). CEST enhancement images upon infusion of glutamine could distinguish tumors that differed in glutamine utilization.

Keywords: Prostate, Cancer, Metabolomics, metabolomic imaging, nuclear magnetic resonance, spectroscopy, prostate cancer, MRI-US fusion, biopsy

Motivation: Evaluations of prostate cancer (PCa) with traditional transrectal ultrasound (TRUS) and multiparametric MRI-ultrasound (mpMRI-US) fusion biopsies may produce false-positives or false-negatives, thereby preventing optimal and timely treatments. 

Goal(s): To evaluate PCa metabolomics from TRUS and fusion biopsy cores using magnetic resonance spectroscopy (MRS) to identify potential metabolomic biomarkers for better characterization of PCa.

Approach: Using ex vivo MRS, we measured 432 prostate biopsy cores from patients suspicious of PCa between 4/2006 and 10/2018. 

Results: MRS metabolomics could differentiate between benign and malignancy, reflect malignant status from benign cores, and allowed for predictions of future PCa from benign biopsies.

Impact: Our results demonstrate that MRS-based metabolomic evaluations have the potential to detect PCa years earlier than standard TRUS and fusion biopic techniques, and improve PCa active surveillance based on prostate biology.

Keywords: Prostate, Prostate

Motivation: Patients on Active Surveillance (AS) for prostate cancer have a high risk of cancer progression to treatment. There is a need for additional tools to risk stratify AS patients.

Goal(s): To evaluate the Habitat Risk Score (HRS) method for automatic identification of lesions for early detection of AS progressors in a prospective trial.

Approach: HRS was assessed in patients that progressed in the 1^st, 2^nd or 3^rd year of AS.

Results: In 40% of the patients, HRS identified a dominant lesion that was not targeted during biopsy. The study illustrates the quantitative power of HRS as compared to PIRADS.

Impact: Integrating Habitat Risk Score (HRS) in Active Surveillance for prostate cancer has the potential to significantly reduce the number of surveillance biopsies. HRS facilitates the detection of progression through assignment of robust biopsy targets and quantification of tumor habitat changes.

Keywords: Probes & Targets, Hyperpolarized MR (Non-Gas)

Motivation: Molecular imaging is a promising methodology for diagnosing cancer and monitoring treatments by noninvasively visualizing the alternations of cancer metabolisms.

Goal(s): A framework for developing novel dissolution Dynamic Nuclear Polarization(dDNP) probes is needed to overcome their limited availabilities for in vivo and clinical applications.

Approach:  dDNP-metabolic MRI successfully monitors therapeutic responses in spatiotemporal enzymatic activities particularly at earlier stages before the volumetric changes can be observed.

Results: In this presentation, we will demonstrate a model case for a rationally designed novel dDNP probe, aminopeptidase-N(CD13), which allows us to detect heterogenetic treatment responses with an anti-angiogenic/antitumor drug, sunitinib, at the earlier stages in tumors. 

Impact: This work exhibits a framework that a rationally designed hyperpolarized MR probe targeted to a highly-selective enzymatic activity, aminopeptidase-N, leads to monitor early therapeutic responses on cancer tissues in vivo and to observe tumor heterogeneity in their treatment responses non-invasively.

Keywords: Biomarkers, Diffusion/other diffusion imaging techniques

Motivation:  Diffusion-weighted imaging (DWI) can help to  predicti rectal cancer prognosis; however, inconsistencies in its effectiveness necessitate exploring advanced DWI models to improve diagnostic accuracy.

Goal(s): We investigated the value of the stretched exponential (SEM), fractional-order calculus (FROC), and continuous-time random-walk (CTRW) models in assessing prognostic factors for rectal cancer.

Approach: This study included 181 rectal cancer patients with using traditional and advanced DWI models to explore correlations between DWI parameters and histopathological indicators.

Results: The parameters of advanced DWI models  were significantly correlated with histopathological prognostic factors. CTRW-α was the superior predictor for histological type and pT stage.

Impact: Our study demonstrates the value of CTRW model in predicting prognostic factors for rectal cancer. Utilizing these noninvasive and accurate advanced DWI models before surgery can help physicians to make appropriate surgical plan to help patients achieve  better prognosis.

Keywords: Biomarkers, Contrast Agent

Motivation: Cellular response to cancer treatment is difficult to track in real time. Standard practice involves immunostaining of a biopsied tumor, but this is severely limited by a number of factors. 

Goal(s): Non-invasive imaging methods such as MRI could obviate the need for biopsies and serve as a biomarker of radiation therapy efficacy. 

Approach: This study aimed to observe macrophage response in a mouse model by use of a fluorine nanoemulsion and ¹⁹F MRI. 

Results: It was shown that macrophage recruitment can be quantified through MRI. Moreover, the findings suggest that macrophage response to radiation therapy is dependent on several factors including tumor origin.

Impact: Our results demonstrate the potential of ¹⁹F MRI to non-invasively track macrophages during radiation therapy and its prognostic value with regards to tumor growth. This technique will be extremely beneficial in future analysis of inflammation’s role in tumor recurrence.