ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Scientific Session: Tumour Diffusion, Perfusion & Vessel Imaging

Tuesday, May 10, 2016
Summit 2
13:30 - 15:30
Moderators: Sungheon Gene Kim, Arvind Pathak

Progressing bevacizumab induced diffusion restriction is associated with coagulative necrosis surrounded by viable tumor and decreased overall survival in recurrent glioblastoma patients
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. LaViolette2,6
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.

In vivo quantification of antimitotic-treatment-induced microstructural changes using temporal diffusion
xiaoyu jiang1, hua li1, jingping Xie1, ping zhao1, junzhong xu1, dineo khabele2, and John Gore1
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.

Quantitative Arterial Spin Labeled (ASL) Perfusion and Diffusion Weighted Imaging (DWI) in Clear Cell Renal Cell Carcinoma: Correlation with Heterogeneous Tumor Vascularity and Cellularity at Histopathology
Qing Yuan1, Payal Kapur2,3, Yue Zhang1, Yin Xi1, Sabina Signoretti4, Ananth Madhuranthakam1,5, Ivan E Dimitrov5,6, Jeffrey A Cadeddu1,3, Vitaly Margulis3, and Ivan Pedrosa1,5
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.

Apparent diffusion coefficient of hyperpolarized lactate reports on lactate production and efflux in renal cell carcinomas
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 Kurhanewicz1
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.

Diagnostic value of intravoxel incoherent motion (IVIM) for differentiating benign and malignant thyroid nodules
hui Tan1, jun CHEN1, YUN-fei ZHA1, liang ZHANG1, jing LU1, Chang-sheng LIU1, and hui LIN2
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.
Combined MRI and optical CT imaging of tumour vasculature in a preclinical model of neuroblastoma
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 Doran1
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.    

Exploring the Relationship between MR-derived Apparent Diffusion Coefficient, Cellularity, and Extracellular Porosity:  A Preliminary Animal Study in Prostate Cancer
Deborah K. Hill1,2, 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. Blackledge3
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.

Non-enhanced Hypercellular Volume in Glioblastoma identified by High b-value Diffusion Weighted Imaging
Yue Cao1,2, Daniel Wahl1, Priyanka Pramanik1, Michelle Kim1, Theodore S Lawrence1, and Hemant Parmar2
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.

Differential tumor perfusion in vivo on Arterial Spin Labeled MRI correlates with heterogeneity in the molecular phenotype of clear cell Renal Cell Carcinoma
Manoj Bhasin1, Rupal Bhatt2, Phillip M Robson3, Deepa Rajamani1, Sabina Signoretti4, David C Alsop3, and Ivan Pedrosa5
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.

DCE-MRI High-resolution Metabolic Prostate Imaging is Insensitive to AIF Uncertainty
Xin Li1, Mark G. Garzotto2,3, 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.

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