Ha Son Nguyen¹, Nelson Milbach², Sarah L Hurrell², Elizabeth Cochran³, Jennifer Connelly⁴, Mona Al-Gizawiy², Joseph Bovi⁵, Scott D Rand², Kathleen M Schmainda², and Peter S. LaViolette^2,6
1Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States, ²Radiology, Medical College of Wisconsin, Milwaukee, WI, United States, ³Pathology, Medical College of Wisconsin, Milwaukee, WI, United States, ⁴Neurology, Medical College of Wisconsin, Milwaukee, WI, United States, ⁵Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States, ⁶Biophysics, Milwaukee, WI, United States

It is the standard of care to initiate bevacizumab therapy for patients with recurrent glioblastoma.  Some patients develop areas of diffusion restriction on diffusion imaging following the onset of therapy. We recruited five patients with this condition to donate their brains postmortem.  A histological analysis was performed and compared to MR images to discover what caused the diffusion restriction.  It was found to be coagulative necrosis surrounded by viable hypercellular tumor.  A second population study shows that patients with progressively expanding diffusion restriction had a significantly lower survival compared to those without.

xiaoyu jiang¹, hua li¹, jingping Xie¹, ping zhao¹, junzhong xu¹, dineo khabele², and John Gore^1
1vanderbilt university institute of imaging science, nashville, TN, United States, ²vanderbilt university, nashville, TN, United States

Reliable and sensitive methods for assessing the response of tumors to treatment are critical in rapid selection of the most appropriate therapy for individual patients, and development of novel therapies. Temporal diffusion spectroscopy, which measures the variation of apparent diffusion coefficient (ADC) over a range of effective diffusion times, is proposed to measure tumor microstructural variations in response to chemotherapy. The proposed method is shown to detect the increase in cell size in response to the antimitotic-treatment in both well-characterized cell culture and solid tumors in vivo. The MR observations are supported by flow cytometric, microscopic, and histological analysis.

Qing Yuan¹, Payal Kapur^2,3, Yue Zhang¹, Yin Xi¹, Sabina Signoretti⁴, Ananth Madhuranthakam^1,5, Ivan E Dimitrov^5,6, Jeffrey A Cadeddu^1,3, Vitaly Margulis³, and Ivan Pedrosa^1,5
1Radiology, UT Southwestern Medical Center, Dallas, TX, United States, ²Pathology, UT Southwestern Medical Center, Dallas, TX, United States, ³Urology, UT Southwestern Medical Center, Dallas, TX, United States, ⁴Pathology, Brigham and Women's Hospital, Boston, MA, United States, ⁵Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, ⁶Philips Medical Systems, Cleveland, OH, United States

We investigated intratumor heterogeneity of perfusion and diffusion in vivo using ASL and DWI in clear cell renal cell carcinoma (ccRCC), and correlated these measures with tumor vascularity and cellularity at histopathology. Focused histopathologic analysis of tumor areas corresponding to high perfusion regions on ASL confirmed higher microvessel density (MVD) and demonstrated higher cellularity compared to tumor areas with low perfusion on ASL. A negative correlation between MRI diffusion measures and tissue cellularity further supports noninvasive MRI techniques as potential imaging biomarker in ccRCC for assessment of heterogeneity in tumor angiogenesis and microenvironment in vivo.

Renuka Sriram¹, Bertram Koelsch¹, Jeremy W Gordon¹, Mark Van Criekinge¹, Celine Baligand¹, Robert A Bok¹, Dan B Vigneron¹, Kayvan R Keshari², Peder E Larson¹, Zhen Jane Wang¹, and John Kurhanewicz^1
1University of California, San Francisco, San Francisco, CA, United States, ²Memorial Sloan-Kettering Cancer Center, New York, NY, United States

This study demonstrated that diffusion weighted HP ¹³C MRI can provide an estimate of the amount of extra- versus intracellular HP ¹³C lactate based on its apparent diffusion coefficient (ADC).   In metastatic renal cell carcinoma, a large portion of the HP ¹³C lactate signal arises from an extracellular lactate pool, based on reliable estimates of ADC in the same cell line in a the MR compatible bioreactor.   The juxtaposition of cells in bioreactor and the in vivo animal model is a powerful tool for interpretation of the hyperpolarized ADC measurements. This unique combination can be further extended to investigate the relationship between lactate transport and tumor metastatic potential.

hui Tan¹, jun CHEN¹, YUN-fei ZHA¹, liang ZHANG¹, jing LU¹, Chang-sheng LIU¹, and hui LIN^2
1Renmin Hospital of Wuhan University, wuhan, China, People's Republic of, ²GE healthcare, shanghai, China, People's Republic of

To preliminary explore the value of intravoxel incoherent motion (IVIM) in the differention between benign and malignant thyroid lesions, 45 patients with 56 thyroid nodules underwent preoperative IVIM (b –1000 s/mm²). Data was postprocessed by IVIM model for quantitation of apparent diffusion coefficient (ADC), perfusion fraction f, diffusivity D and pseudo diffusivity D*. Significant intergroup difference was observed in ADC, D, D*, and f, the f value is the most valuable parameter in identifying the malignant from benign nodules. The IVIM sequence has potential to differentiate the benign from malignant thyroid nodules.
 

Ciara M McErlean¹, Yann Jamin¹, Jessica KR Boult¹, Alexander Koers¹, Laura S Danielson¹, David J Collins¹, Martin O Leach¹, Simon P Robinson¹, and Simon J Doran^1
1Institute of Cancer Research, London, United Kingdom

This study compares MRI functional measurements of the vasculature in a preclinical model of neuroblastoma with ex vivo optical CT  high-resolution 3D imaging of the functional vasculature using India ink staining. MRI showed a heterogeneously perfused tumour with high fractional blood volume and vessel size index, characteristic of hypervascular neuroblastoma.  The high resolution optical CT images allowed visualisation of individual vessels and corroborated the MRI findings. With improved registration, optical CT could help validate MRI functional biomarkers of the vasculature and accelerate both our understanding of vessel biology and the evaluation of vascular-targeted treatment in cancer and other vascular-related pathologies.    

Deborah K. Hill^1,2, Andreas Heindl³, Daniel N. Rodrigues³, Øystein Størkersen², Yinyin Yuan³, Siver A. Moestue ^1,2, Martin O. Leach³, Tone F. Bathen¹, David J. Collins³, and Matthew D. Blackledge^3
1Norwegian University of Science and Technology, Trondheim, Norway, ²St. Olavs University Hospital, Trondheim, Norway, ³The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom

An increased ADC can imply reduced cellularity; DWI is considered a useful tool for assessing tumour treatment response, although there is little validation of this relationship in cancer. We compared ADC, cellularity, and extracellular porosity using a transgenic adenocarcinoma of the mouse prostate model. ADC values were derived from DWI data, and cellularity was assessed from histology using novel visualisation and segmentation tools. We investigated the relationship between extracellular porosity and ADC, and validated our findings using cell segmentation analysis of histology slides. This analysis is useful to inform on tissue cellularity for cases where histology samples are not available.

Yue Cao^1,2, Daniel Wahl¹, Priyanka Pramanik¹, Michelle Kim¹, Theodore S Lawrence¹, and Hemant Parmar^2
1Radiaiton Oncology, University of Michigan, Ann Arbor, MI, United States, ²Radiology, University of Michigan, Ann Arbor, MI, United States

It is a challenge to differentiate non-enhanced components of glioblastoma (GBM) from edema and normal tissue using conventional MRI.  The ill-differentiation could lead to inadequate treatment for GBM by surgery and radiation therapy.  This study evaluated the enhanced and non-enhanced hypercellular volume (HCV) of GBM identified by high b-value diffusion weighted (DW) imaging with gross tumor volume defined on post-Gd T1 weighted images, abnormality volume on T2 FLAIR images, high dose coverage planned according to conventional MRI, and progression.  This study found that the HCV was an aggressive component of GBM and predicted progression free survival.

Manoj Bhasin¹, Rupal Bhatt², Phillip M Robson³, Deepa Rajamani¹, Sabina Signoretti⁴, David C Alsop³, and Ivan Pedrosa^5
1Division of Interdisciplinary Medicine & Biotechnology, and Genomics, Proteomics, Bioinformatics and Systems Biology Center, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States, ²Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, MA, United States, ³Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, United States,⁴Pathology, Brigam and Women's Hospital, Boston, MA, United States, ⁵Radiology, UT Southwestern Medical Center, Dallas, TX, United States

We used Arterial Spin Labeled (ASL) MRI to explore the association between heterogeneous in vivo perfusion in clear cell renal cell carcinoma (ccRCC) and the underlying genomic profile to identify key genes linked to tumor angiogenesis. Ephrin-A5 (EFNA5) expression correlated with ASL perfusion (R2 = 0.504, P value= .002) and exhibited highest significant differences between low and high perfusion (Fold Change = 2.88, P value < 0.02). Higher expression of EFNA5 is associated with poor 3 and 5 years survival (P = 0.0009). We propose MRI-based targeted tissue sampling to characterize the heterogeneous genetic alterations driving angiogenesis in ccRCC.

Xin Li¹, Mark G. Garzotto^2,3, Fergus V. Coakley⁴, Brendan Moloney¹, William J. Woodward¹, Yiyi Chen⁵, Wei Huang¹, William D. Rooney¹, and Charles S. Springer, Jr.^1
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, ²Portland VA Medical Center, Portland, OR, United States, ³Urology, Oregon Health & Science University, Portland, OR, United States, ⁴Department of Diagnostic Radiology, Oregon Health & Science University, Portland, OR, United States, ⁵Division of Biostatistics, Dept. of Public Health and Preventive Medicine, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, United States

Accurate arterial input function (AIF) measurement in Dynamic Contrast Enhanced MRI (DCE-MRI) remains challenging. This hinders DCE-MRI’s wider adoption.  Since the contrast reagent (CR) is detected indirectly through water proton R₁ relaxation rate constant change, DCE-MRI intrinsically works as a dual-probe (CR and water) method.  In this study, we demonstrate that while the common pharmacokinetic parameters associated with CR extravasation are highly sensitive to AIF accuracy, the transcytolemmal water exchange parameter is not.  With the recent correlation of water exchange kinetics and cellular metabolic activity, this current work demonstrates the practicability of  high-resolution metabolic imaging of the prostate.