Stefan Posse¹, Kishore Vakamudi¹, Bruno Sa De La Rocque Guimaraes¹, Rex Jung², and Muhammad Omar Chohan^2
1Neurology, University of New Mexico, Albuquerque, NM, United States, ²Neurosurgery, University of New Mexico, Albuquerque, NM, United States

We investigated presurgical resting-state fMRI (rsfMRI) in 9 patients with brain tumors using high-speed multiband-EPI (TR:400ms) with real-time data quality monitoring for seed-based localization of sensorimotor and language networks. The Euclidean distance between intra-operative electrocortical-stimulation (ECS) and rsfMRI connectivity and task-activation in motor cortex, Broca’s and Wernicke’s areas was 5-13mm, except for discordant rsfMRI localization of Wernicke’s area in one patient due to possible altered neurovascular coupling. A secondary objective was to accelerate encoding using echo-volumar-imaging. This study demonstrates the potential of high-speed rsfMRI for presurgical mapping and clinically-acceptable concordance with task-based fMRI and ECS localization.

Eva Oberacker¹, Cecilia Diesch¹, Jacek Nadobny², Andre Kuehne³, Thomas Wilhelm Eigentler¹, Pirus Ghadjar², Peter Wust², and Thoralf Niendorf^1,3,4
1Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, ²Clinic for Radiation Oncology, Charité Universitätsmedizin, Berlin, Germany, ³MRI.TOOLS GmbH, Berlin, Germany, ⁴Experimental and Clinical Research Center (ECRC), joint cooperation between the Charité Medical Faculty and the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany

Ultrahigh-field MR employs higher radio frequencies (RF) than conventional MR and has unique potential to provide focal temperature manipulation and high resolution imaging in an integrated device (ThermalMR). The advantage of integrated therapy monitoring and guidance benefits thermal interventions in brain tumor treatments. To approach this goal this work examines the inter-patient variability in a heterogeneous group of glioma multiforme patients using EMF simulations.  Our findings provide useful indicators as potential patient inclusion criteria for thermal treatment of brain tumors and form the technological basis for treatment planning and RF applicator developments en route to clinical applications of Thermal MR.  

Uwe Himmelreich¹, Matteo Riva², Sarah Belderbos¹, Roxanne Wouters², Akila Weerasekera¹, Thais Baert², Willy Gsell¹, and An Coosemans^2
1Biomedical MRI, University of Leuven, Leuven, Belgium, ²Department of Oncology, University of Leuven, Leuven, Belgium

Several promising treatments against high-grade gliomas (HGGs) failed to provide significant benefit when translated from the preclinical setting to patients. Improving animal models is fundamental to overcome this translational gap. We have developed and comprehensively characterized in-vivo model based on the orthotopic implantation of CT-2A cells cultured in neurospheres (NS). Anatomical, metabolic (MRS) and perfusion MRI indicated that CT-2A NS-derived tumors showed a more HGG-like behavior, which was supported by survival data, increased glioma stem cell population and enhanced neoangiogenesis. Because of these specific features, the CT-2A NS-derived model represents a high-translational platform for the search of new HGG treatments.

Rachel W Chan¹, Sten Myrehaug², Greg J Stanisz^1,3,4, James Stewart², Mark Ruschin², Arjun Sahgal^2,3, and Angus Z Lau^1,3
1Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ²Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, ³Medical Biophysics, University of Toronto, Toronto, ON, Canada, ⁴Department of Neurosurgery and Pediatric Neurosurgery, Medical University, Lublin, Poland

This study aims to quantify the MT and CEST parameters in glioblastoma at 1.5T over four time points of chemoradiation. Previous approaches to quantify the MT/CEST signal in terms of response to treatment were at higher field strengths. Additionally, we analyzed different subregions within the clinical target volume and gross tumor volume, generated by thresholding based on the T₁-weighted, FLAIR and DWI scans, for comparing the MT/CEST parameters between the early and late tumor progression. Results indicated that MT/CEST at 1.5T can be used for monitoring therapy and that the results depend on the specific tumor region analyzed.

Ruiliang Bai¹, Bao Wang², Yinhang Jia¹, Zhaoqing Li³, Yi-Cheng Hsu⁴, Charles S. Springer Jr.⁵, and Yingchao Liu^6
1Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China, ²Department of Radiology, Shandong University Qilu Hospital, Jinan, China, ³College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China, ⁴MR Collaboration, Siemens Healthcare, Shanghai, China, ⁵Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, ⁶Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University, Jinan, China

The [Shutter-Speed-Model-Dynamic-Contrast-Enhanced] SSM-DCE-MRI pharmacokinetic analysis has a metabolic dimension. However, SSM must be applied thoughtfully, especially in Glioblastoma multiforme [GBM], because of strong tissue vascular heterogeneity across the brain field-of-view Here, we present a method to select the appropriate SSM-DCE-MRI version to analyze such tissue, on a pixel-by-pixel basis.  The supra-intensive parameters, vascular water efflux (k_bo), cellular water efflux (k_io), and vascular CA efflux (k_pe) rate constants could be reliably determined.  Pilot data on one recurrent and one pre-diagnosis GBM patient are presented to demonstrate method performance.  

Maria Ljungberg^1,2, Erik Fernström³, Oscar Jalnefjord^1,2, Mikael Montelius¹, Thomas Björk-Eriksson³, Marie Kalm⁴, and Marianne Jarfelt^5
1Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Göteborg, Sweden, ²Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Göteborg, Sweden, ³Oncology, Institute of Clinical Sciences Sahlgrenska Academy Gothenburg University, Göteborg, Sweden, ⁴Health and Rehabilitation, Institute of neuroscience and physiology, Sahlgrenska Academy Gothenburg University, Göteborg, Sweden, ⁵Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy Gothenburg University, Göteborg, Sweden

Modern cranial radiotherapy (CRT) achieves high targeted doses of radiation to brain tumours, which has resulted in an increased population of long-term survivors of childhood cancer. Unfortunately, the CRT cause radiation damage to the healthy brain which results in cognitive deficits. In a group of adult childhood cancer survivors lower ratios of tNAA/tCho, Glu/tCho and Glu/tCr were obtained in the hippocampus for the patient group that received highest radiation doses to target volume as compared to the group that did not receive any CRT, indicating a still ongoing process of e.g inflammation, re-myelination and gliosis due to CRT

Nobuhiro Nitta¹, Yoichi Takakusagi¹, Daisuke Kokuryo², Sayaka Shibata¹, Akihiro Tomita³, Tatsuya Higashi¹, Ichio Aoki¹, and Masafumi Harada^4
1Department of Molecular Imaging and Theranostics, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan, ²Graduate School of System Informatics, Kobe University, Hyogo, Japan, ³Department of Hematology, Fujita Health University School of Medicine, Aichi, Japan, ⁴Graduate School of Medicine, Tokushima University, Tokushima, Japan

The enhanced permeability and retention (EPR) effect depends on nanoparticle properties and tumor/vessel conditions. We aimed to develop a tumor vasculature evaluation method and high-resolution nanoparticle-delivery imaging technique using magnetic resonance micro-imaging technology and a gadolinium (Gd)-dendron assembled liposomal contrast agent. We achieved 50-μm isotropic MR angiography with clear visualization of tumor micro-vessel structure. The Gd-liposome-enhanced MR micro-imaging revealed differences in the vascular structures between two different types of grafted mice models. The MR micro-imaging methods facilitate the evaluation of intratumoral vascularization patterns, the quantitative assessment of vascular-properties that alter tumor malignancy, particle retentivity, and the effects of treatment.

Jianbo Cao¹, Stephen Pickup¹, Hee Kwon Song¹, and Rong Zhou^1,2
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States

Genetically engineered mouse (GEM) model of pancreatic ductal adenocarcinoma (PDA) recapitulates a dense stroma exhibited in human disease and is thus relevant for testing stroma-directed drugs. However, the lesion location makes it highly susceptible to motion. We present a multi-slice 2D saturation-recovery technique using golden-angle radial k-space sampling combined with KWIC reconstruction for DCE-MRI of PDA. This method minimizes respiration motion artefacts in PDA tumors and increases the effective temporal resolution of the AIF. K^trans and k_ep maps derived from PK model fitting of DCE series exhibit adequate spatial resolution to reveal permeability and perfusion heterogeneity in the PDA tumor.

Shun Kishimoto¹, Nallathamby Devasahayam¹, Yu Saida¹, Yasunori Otowa¹, Kazutoshi Yamamoto¹, Jeffrey R Brender¹, and Murali C Krishna^1
1NCI, Bethesda, MD, United States

TH-302 is designed to release cytotoxic bromo-isophosphoramide (Br-IPM) moiety in hypoxic microenvironment. Therefore, this drug preferentially attacks the hypoxic region in cancer where other standard anti-cancer treatment such as chemotherapy and radiation therapy are ineffective. Here, we monitored the change in tumor hypoxia and perfusion in response to TH-302 treatment by EPR oximetry and DCE MRI using two pancreatic ductal adenocarcinoma xenograft models. The result showed improved oxygenation only in treatment sensitive MIA Paca-2 tumors without modulating tumor blood perfusion, suggesting that intratumor pO2 is a useful biomarker to evaluate treatment response to TH-302.

Daniel Coman¹, Ryan J Slovak^2,3, Fahmeed Hyder^1,4,5, and Hyun S Kim^1,2,5,6
1Radiology & Biomedical Imaging, Division of Bioimaging Sciences, Yale University School of Medicine, New Haven, CT, United States, ²Radiology & Biomedical Imaging, Section of Interventional Radiology, Yale University School of Medicine, New Haven, CT, United States, ³University of Connecticut School of Medicine, Farmington, CT, United States, ⁴Department of Biomedical Engineering, Yale University School of Medicine, New Haven, CT, United States, ⁵Yale Cancer Center, Yale University School of Medicine, New Haven, CT, United States, ⁶Department of Internal Medicine, Section of Medical Oncology, Yale University School of Medicine, New Haven, CT, United States

Acidification of tumor microenvironment is associated with aggressive tumor growth and facilitate resistance to anti-cancer therapies. Extracellular pH (pH_e) mapping with BIRDS is used to differentiate ablated and non-ablated tumors in the setting of systemic immunotherapy of murine colorectal cancer. Combination of Cryoablation with Dual Immune Checkpoint Blockade (DICB) resulted in a significant pH_e increase compared to control tumors. This work demonstrates the feasibility of measuring pH_e with BIRDS in a murine colorectal cancer model. pH_e imaging  could serve as a non-invasive imaging biomarker for tumor microenvironment assessment and monitoring of metabolic changes after immuno-thermal ablation therapy.

Yuki Arita^1,2, Yuma Waseda³, Soichiro Yoshida^2,3, Taro Takahara^2,4, Chikako Ishii², Thomas C Kwee⁵, Ryota Ishii⁶, Shigeo Okuda¹, Yasuhisa Fujii³, and Masahiro Jinzaki^1
1Department of Radiology, Keio University School of Medicine, Tokyo, Japan, ²Department of Radiology, Advanced Imaging Center Yaesu Clinic, Tokyo, Japan, ³Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan, ⁴Department of Biomedical engineering, Tokai University School of Engineering, Kanagawa, Japan, ⁵Department of Radiology, Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, Netherlands, ⁶Department of Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan

The purpose of this study is to determine the value of applying computed DWI to a whole-body MRI/DWI protocol to acquire computed high b-value (2000 s/mm²) diffusion-weighted images for local prostate cancer evaluation. Based on the results, computed diffusion-weighted images obtained from whole-body MRI provide a similar diagnostic performance compared to  pelvic bi-parametric MRI for the detection of primary prostate cancer. Computed DWI is a straightforward postprocessing technique without the need for additional image acquisition time. It can be recommended for use in routine clinical practice in whole-body MRI protocols for concurrent evaluation of primary and metastatic prostate cancer.

Soichiro Yoshida¹, Taro Takahara², Yuki Arita^3,4, Chikako Ishii⁴, Kazuma Toda⁵, Kazuma Toda⁵, Tsuyoshi Sakamoto⁶, Toshiki Kijima¹, Minato Yokoyama¹, Junichiro Ishioka¹, Yoh Matsuoka¹, Kazutaka Saito¹, Ryoichi Yoshimura⁵, and Yasuhisa Fujii^1
1Urology, Tokyo Medical and Dental University, Tokyo, Japan, ²Biomedical Engineering, Tokai University School of Engineering, Kanagawa, Japan, ³Radiology, Keio University School of Medicine, Tokyo, Japan, ⁴Radiology, Advanced Imaging Center, Yaesu Clinic, Tokyo, Japan, ⁵Radiation Therapeutics and Oncology, Tokyo Medical and Dental University, Tokyo, Japan, ⁶PixSpace, Ltd., Fukuoka, Japan

Locoregional therapy for oligometastatic prostate cancer has generated great interest. However, the benefit for castration-resistant prostate cancer (CRPC) has not been fully demonstrated. According to the current study, whole body-MRI incorporating DWI identified a substantial number of oligo-progressive CRPC patients (OP-CRPC) with a number of progressive lesions 3 or less. Progressive site-directed therapy (PSDT) to OP-CRPC provided a high treatment effect in terms of prostate-specific antigen (PSA) response, especially for patients with longer PSA-doubling time. Furthermore, this study identified the site-dependencies of the PSDT treatment effect; patients whose progressive site was localized in the pelvis were good candidates for PSDT.

Akanksha Bhargava¹, Manisha Aggarwal¹, and Arvind Pathak^1
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States

Preclinical imaging methods such as magnetic resonance microscopy (µMRI), micro-computed tomography (µCT) and optical techniques such as multiphoton microscopy (MPM) have been instrumental in advancing our understanding of the role of vasculature in cancer1. However, integrating vascular microenvironmental data across modalities and spatial scales for novel “image-based” cancer systems biology applications2 remains a challenge. Therefore, we developed a multimodality imaging pipeline that achieves multiscale data integration, image co-registration and results in the generation of “cancer atlases” for systems and computational biology applications.

Konstantinos Zormpas-Petridis¹, Matthew D. Blackledge¹, Louis Chesler², Yinyin Yuan³, Simon P. Robinson¹, and Yann Jamin^1
1Radiotherapy and Imaging, Institute of Cancer Research, London, Sutton, United Kingdom, ²Clinical studies, Institute of Cancer Research, London, Sutton, United Kingdom, ³Molecular pathology, Institute of Cancer Research, London, Sutton, United Kingdom

We use Gaussian mixture modeling, computational pathology and MRI-histopathology registered datasets to evaluate i) the sensitivity of diffusion-weighted imaging to the rich histopathology of childhood neuroblastoma and ii) the sensitivity of the derived apparent diffusion coefficient, ADC, as a biomarker of response to a potent MYCN-targeted small molecule inhibitor in the Th-MYCN mouse, a faithful model of high-risk MYCN-driven disease.

Sai Man Cheung¹, Ehab Husain², Yazan Masannat³, Klaus Wahle⁴, Steven Heys³, and Jiabao He^1
1Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, United Kingdom, ²Pathology Department, Aberdeen Royal Infirmary, Aberdeen, United Kingdom, ³Breast Unit, Aberdeen Royal Infirmary, Aberdeen, United Kingdom, ⁴Institute of Pharmacy and Biological Sciences, University of Strathclyde, Glasgow, United Kingdom

Upregulation of aerobic glycolysis and an elevated lactate accumulation have been linked to tumour aggressiveness. However, current evidence drawn from cell culture and small animal models remains controversial. Since lactate and lipid share the same spectral frequency, conventional MRS is inadequate in quantifying lactate under overwhelming lipid signal. Double quantum filtered (DQF) MRS allows excellent suppression of lipid signal from adipose breast tissues. We examined prognostic role of lactate concentration through a cross sectional study in grade II and III whole tumours freshly excised from patients with breast cancer using DQF MRS for the quantification of lactate concentration.