Hana Lahrech¹, Manuel Petit¹, Sandra Pierre¹, Maxime Leclercq¹, Lionel Marc Broche², and François Berger^1
1BrainTech Lab INSERM U1205, Grenoble, France, ²University of Aberdeen, Aberdeen, United Kingdom

In FFC-NMR, R₁-dispersion curves of biological systems frequently show quadrupolar peaks (QP) between 1.5 and 3.5 MHz that correspond to the cross relaxation of water ¹H and protein ¹⁴N. QP of glioma invasion tissues (Glio6 and Glio96 mouse models) and of high glioma proliferation (U87 model) were acquired ex vivo and compared to cell pellets in vitro, showing significant differences. This result suggests that QP signals are intracellular, a result which was confirmed by measurements of cells after trypsin treatment which showed unchanged QP amplitude. This result highlights the potential of the QPs as an intracellular biomarker of glioma invasion.

Tao Lin¹, Jiazheng Wang², Peng Sun², Lihua Chen¹, Qingwei Song¹, Renwang Pu¹, Ying Zhao¹, Xue Ren¹, Qihao Xu¹, and Ailian Liu^1
1The First Affiliated Hospital of Dalian Medical University, Dalian, China, ²Philips Healthcare, Beijing, China

Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) are the most common types of primary liver cancer, which differ greatly in terms of pathogenesis, biological behavior, histological morphology, treatment, and prognosis. This retrospective study revealed that APT combined with quantitative DIXON technique could improve the performance for differentiating HCC from ICC.

Matteo Figini¹, Antonella Castellano², Michele Bailo³, Marcella Callea⁴, Valentina Pieri², Marcello Cadioli⁵, Marco Palombo^1,6,7, Pietro Mortini³, Andrea Falini², Daniel C Alexander¹, Mara Cercignani^6,8, and Eleftheria Panagiotaki^1
1Centre for Medical Image Computing, Computer Science Department, University College London, London, United Kingdom, ²Neuroradiology Unit and CERMAC, Vita-Salute San Raffaele University and IRCCS Ospedale San Raffaele, Milan, Italy, ³Department of Neurosurgery and Gamma Knife Radiosurgery, Vita-Salute San Raffaele University and IRCCS Ospedale San Raffaele, Milan, Italy, ⁴Pathology Unit, IRCCS Ospedale San Raffaele, Milan, Italy, ⁵Philips Healthcare, Milan, Italy, ⁶Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, United Kingdom, ⁷School of Computer Science and Informatics, Cardiff University, Cardiff, United Kingdom, ⁸Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, United Kingdom

We recently adapted the VERDICT framework to characterize both the core and peritumoural areas of brain tumours. We report here its first clinical application in the differentiation of brain tumour histotypes. Comparing groups of lesions with increasing aggressiveness (from lower to higher grades to metastases) we observed a significant increase in the intracellular and vascular fraction in the lesion core. VERDICT maps matched the features showed by histopathology in lower grades and in metastases; in the most heterogeneous higher grades, VERDICT maps showed differences between subregions compatible with histopathology results in multiple biopsy samples.

Nikolaus von Knebel Doeberitz¹, Florian Kroh², Johannes Breitling², Srdjan Maksimovic¹, Laila Koenig³, Juergen Debus^3,4, Peter Bachert^2,5, Heinz-Peter Schlemmer^1,6, Mark E. Ladd^2,5,6, Steffen Goerke², and Daniel Paech^1,7
1Division of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ³Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany, ⁴Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ⁵Department of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany, ⁶Faculty of Medicine, University of Heidelberg, Heidelberg, Germany, ⁷Department of Neuroradiology, Bonn University Hospital, Bonn, Germany

In this interim analysis we compared in patients with gliomas the ability of asymmetry-based amide proton transfer weighted (APTw) imaging with Lorentzian-fit-based relaxation-compensated CEST-MRI (MTR_Rex) of the APT, rNOE and MT signal to differentiate disease progression from treatment induced changes six weeks after completion of radiotherapy. In progressive gliomas, APTw displayed significantly higher signal intensities in contrast enhancing tissue compared to non-progressive gliomas with an AUC of 0.77 in receiver operator characteristic analyses (p 0.03). MT_MTRrex showed a trend towards higher signal intensities in progressive tumors. All CEST metrics displayed significant differences in white and gray brain matter signal intensities.

Amita Vaidya¹, Aman Shankardass¹, Megan Buford¹, Ryan Hall¹, and Zheng-Rong Lu^1
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States

C-X-C motif chemokine receptor 2 (CXCR2) expression is associated with high-grade and advanced prostate cancer. LNCaP-CXCR2+ prostate cancer cells with stable expression of CXCR2 exhibited mesenchymal features and became more aggressive with elevated expression of an ECM oncoprotein EDB-FN as compared to the slow-growing parental cell line, LNCaP. MRMI of EDB-FN with a targeted contrast agent MT218 resulted in significant increase of T1-weighted contrast enhancement in LNCaP-CXCR2+ prostate tumors as compared to the LNCaP tumors in mice. The results suggest that MRMI of EDB-FN has the potential to provide non-invasive active surveillance of low-grade prostate cancer.

Savannah R Duenweg¹, Xi Fang², Samuel A Bobholz¹, Allison K Lowman³, Michael Brehler³, Fitzgerald Kyereme³, Kenneth A Iczkowski⁴, Kenneth Jacobsohn⁵, Anjishnu Banerjee², and Peter S LaViolette^3,6
1Biophysics, Medical College of Wisconsin, Wauwatosa, WI, United States, ²Biostatistics, Medical College of Wisconsin, Wauwatosa, WI, United States, ³Radiology, Medical College of Wisconsin, Wauwatosa, WI, United States, ⁴Pathology, Medical College of Wisconsin, Wauwatosa, WI, United States, ⁵Urology, Medical College of Wisconsin, Wauwatosa, WI, United States, ⁶Biomedical Engineering, Medical College of Wisconsin, Wauwatosa, WI, United States

This study used prostate histology and multi-parametric magnetic resonance imaging (MP-MRI) to evaluate diffusion differences in Gleason pattern 4 gland morphology. After surgery, tissue was sliced using slicing jigs, annotated by a board-certified pathologist, and digitally contoured to differentiate lumen and epithelium. Slides were co-registered to the T2-weighted MRI scan. Two linear mixed models were fitted to the MP-MRI data to consider the different hierarchical structures. Model (1) considers patient as random effect, and Model (2) adds a nested effect for slide. We found that cribriform glands were more diffusion restricted than fused glands in Gleason Grade 4 tumors. 

Emma L Reeves¹, Jin Li¹, Konstantinos Zormpas-Petridis¹, James Sullivan², Craig Cummings¹, Barbara Blouw³, David Kang³, Ralph Sinkus⁴, Jeffrey C Bamber¹, Yann Jamin¹, and Simon P Robinson^1
1Radiotherapy & Imaging, Institute of Cancer Research, London, United Kingdom, ²Royal Marsden NHS Foundation Trust, London, United Kingdom, ³Halozyme Therapeutics, San Diego, CA, United States, ⁴Life Sciences and Medicine, King's College London, London, United Kingdom

The impact of HA on tumour characteristics measured by MRI/E is not fully understood. We evaluated relationships between MRI biomarkers and histology in saline (HA present) and PEGPH20 treated (HA absent) breast tumours. ADC had the strongest association with HA, reaffirming that ADC is the most sensitive biomarker of tumour response to PEGPH20. MTR negatively correlated with HA, likely due to a HA-mediated dilution of MT-inducing components including collagen. MRE-derived elasticity (G_d) did not directly correlate with HA, however, HA degradation reduced the contribution of collagen to tumour viscoelasticity and may shift the sensitivity of G_d to the cellular compartment.

Akane Ohashi¹, Masako Kataoka², Mami Iima², Maya Honda³, Rie Ota², Yuta Urushibata ⁴, Dominic Marcel Nickel⁵, Masakazu Toi⁶, Sophia Zackrisson¹, and Yuji Nakamoto^2
1Translational Medicine, Diagnostic Radiology, Lund University, Skåne University Hospital, Malmö, Sweden, ²Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan, ³Diagnostic Radiology, Kansai Electric Power Hospital, Osaka, Japan, ⁴Siemens Healthcare K.K., Tokyo, Japan, ⁵Siemens Healthcare GmbH, Erlangen, Germany, ⁶Breast Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan

To evaluate the possibility of replacing conventional DCE MRI with UF-DCE MRI, we assessed the concordance of morphological information of the mass lesions between UF-DCE MRI and the early phase of DCE MRI. The size and shape showed excellent concordance between the two phases, while UF-DCE MRI tended to show circumscribed margin and homogeneous enhancement. In a sub-analysis, luminal subtypes demonstrated smaller size with homogeneous enhancement pattern compared with non-luminal subtypes. Predictive model for luminal subtype using the two parameters resulted in the AUC of 0.68, 0.72, for UF-DCE MRI and the early phase of DCE MRI, respectively (p=0.23).